ORIGINAL ARTICLE Seroprevalence of transfusion-transmissible infectious agents among volunteer blood donors between 2006 and 2012 in Zhejiang, China Xiaofan Zheng1,2,3, Wei Ding2,3, Gan Li2,3, Yaling Wu2,3, Danxiao Wu2,3, Hong Zhu2,3, Ji He2,3, Bin Wang4, Longyou Zhao5, Faming Zhu2,3, Hangjun Lv1,2,3 Wenzhou Medical University, Wenzhou; 2Blood Centre of Zhejiang Province, Hangzhou; 3Key Laboratory of Blood Safety Research, Ministry of Health, Hangzhou; 4Wenzhou Blood Station, Wenzhou; 5Lishui Blood Station, Lishui, Zhejiang, China 1
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Background. The high prevalence of hepatitis B and C viruses (HBV and HCV), paralleling the growing epidemic of human immunodeficiency virus (HIV) and Treponema pallidum (TP) infections in the general population, poses a great threat to blood safety in China. This study investigated the prevalence of serological markers for causative agents of transfusion-transmissible infections (TTI), i.e. HBV, HCV, HIV and TP, among volunteer blood donors in five cities/regions of Zhejiang Province, China. Material and methods. We investigated whole blood and apheresis donations collected at the Blood Services in five cities/regions in Zhejiang Province between January 1, 2006 and December 31, 2012. Two rounds of serological testing were performed for HBsAg, anti-HCV, anti-HIV1/2 and anti-TP using different kits. The rates of serological positivity were calculated and further analysis was performed to examine the association between donors' characteristics and seroprevalence. Results. Of the 1,615,120 donations, approximately 40% came from first-time donors and 60% from repeat donors. The overall seroprevalence rates of HBV, HCV, HIV and TP were 0.51%, 0.25%, 0.15% and 0.52%, respectively. The overall prevalences of HCV and HIV remained relatively steady, whereas the prevalence of TP increased sharply after 2010. However, the prevalence of TTI agents varied among volunteer blood donors in different cities/regions and demographic groups. Discussion. We collected data on the seroprevalence of TTI agents among volunteer blood donors. Although the risk of TTI is low in China compared to that in some developing countries, sensitive screening methods and recruitment of regular donors are still very important for blood safety and availability.
Introduction
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Keywords: transfusion-transmissible infection, blood donor, seroprevalence.
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Despite significant progress made over the last few decades in the prevention of transfusion-transmissible infections (TTI) through blood transfusion, transmission of pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Treponema pallidum (TP) via transfusion still poses a great threat to blood safety. In the global view, the risk of TTI has been drastically reduced by the introduction of routine donor laboratory screening for blood-borne pathogens and by volunteer donations1,2. As a consequence of continuous implementation and improvement of more sensitive serological methods and nucleic acid amplification tests (NAT), in the European Union and the United States the residual risk of HIV and HCV among all allogeneic donations is currently below 1 per 1 million donations, and that of HBV is close to 1 per 300,000 donations3,4. In another study, estimates of residual risk among repeat apheresis donors in the United
States between 2007 and 2008 were 1:1.0 million for HIV, 1:3.2 million for HCV, and 1:200,000 for HBV5. Furthermore, one recent study in the United States showed that with the addition of minipool-NAT, and resulting 8.8-day window-period reduction, residual risks for HBV decreased from 1:765,000 to 1:1,006,0006. In China and other developing countries, the risks of TTI are higher than those in above-mentioned developed nations7-10. With the rapid growth of the Chinese economy in the last 30 years, the blood transfusion services in China have experienced great transformation and development. By the end of 2012, there were 531 Blood Centres/Banks in China, organised in three levels: provincial, regional and county Blood Services (according to the Chinese Health Statistical Digest, 2013-2014 issued by the National Health and Family Planning Commission of People's Republic of China: http://www.nhfpc.gov.cn/ewebeditor/uploadf ile/2014/04/20140430131845405.pdf, last accessed on 01/09/2014). Since the Blood Donation Law came into
Blood Transfus 2015; 13; 401-10 DOI 10.2450/2015.0271-14 © SIMTI Servizi Srl
401 All rights reserved - For personal use only No other uses without permission
Zheng X et al
iz i
Sr l
Our study population consisted of all whole blood and apheresis donors in the five cities/ regions from January 2006 through December 2012. All the candidate donors underwent pre-donation screening. The whole process included a health history questionnaire, a brief physical examination and rapid predonation testing. If donors reported in questionnaire that they had been diagnosed as having HIV infection, syphilis, or any other sexually transmitted disease or viral hepatitis, they were permanently deferred. Next, the donors had to pass a physical examination regarding body weight and blood pressure. Rapid pre-donation testing included haemoglobin level, hepatitis B virus surface antigen (HBsAg), alanine aminotransferase level and determination of ABO blood group. Potential donors with a low haemoglobin level (lower than 120 g/L in males; in females, lower than 110 g/L before June 2012 and lower than 115 g/L since June 2012), abnormal alanine aminotransferase or positive HBsAg results were temporarily deferred. All successful donations then underwent two rounds of routine serological testing for HBsAg, anti-HCV, antiHIV1/2 and anti-TP by two different reagents according to the manufacturers' instructions; both imported and domestic testing kits, approved and licensed by the Chinese State Food and Drug Administration, were used (listed in Table I). We used a dual screening strategy to test donations. If the test results from either assay in the strategy were reactive, the sample was judged positive, the donation was discarded and the donor was permanently deferred. We extracted all data
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Materials and methods
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effect in 1998, many changes have been made in the field of blood banking in China and blood collection has been successfully transformed from paid and family member donations to voluntary donations. Compared to 1998, when paid donations or donations from family members made up 80% of its blood supplies, China has achieved 98.5% voluntary donations in just 10 years (http://www. who.int/mediacentre/news/releases/2008/pr18/en/, last accessed on 01/09/2014). Currently, the blood donation rate is only 9‰ of the whole population in China, which is much lower than the desired rate indicated by the World Health Organisation (WHO): 10-30‰. Although the volume of blood collected has increased dramatically, the increase in the blood supply has not kept pace with the increasing clinical demand for blood in China. Furthermore, besides the problem of blood availability, there are great challenges in ensuring blood safety. The high prevalences of HBV and HCV, paralleling the growing epidemics of HIV and TP in the general Chinese population, are at the basis of these challenges. While there has been some research focusing on the prevalence of these infectious diseases in the general Chinese population, epidemiological data on the seroprevalence of TTI agents among Chinese volunteer blood donors are still limited despite recent publications by Wang et al9,10. In this study, we investigated the seroprevalence of transfusion-transmissible pathogenic agents including HBV, HCV, HIV and TP among blood donors from 2006 to 2012 in Zhejiang Province, which is one of the most prosperous areas in China.
Table I - HBsAg, anti-HCV, anti-HIV1/2 and anti-TP reagents used for screening donors. Kit name
Company
Diagnostic kit for HBV surface antigen (ELISA)
InTec Products, Inc. (Xiamen, China); Ke-Hua BIO-Engineering Co., Ltd. (Shanghai, China); BioMérieux Clinical Diagnostics (Shanghai, China); Murex Biotech Limited (Dartford, UK)
Diagnostic kit for antibody to HCV (ELISA)
InTec Products, Inc. (Xiamen, China); Ke-Hua BIO-Engineering Co., Ltd. (Shanghai, China); Ortho-Clinical Diagnostics, Inc. (New Jersey, USA)
Diagnostic kit for antibody to HIV-1/2 (sandwich ELISA)
Livzon Diagnostics Inc. (Zhuhai, China); BioMérieux Clinical Diagnostics (Shanghai, China); Bio-Rad (Marnes-la-Coquette, France)
Diagnostic kit for antibody to Treponema pallidum (ELISA)
InTec Products, Inc. (Xiamen, China); Wan-Tai Biological Pharmacy Enterprise Co., Ltd. (Beijing, China)
©
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Participants and study procedure Zhejiang Province is located in the southern part of the Yangtze River Delta on the southeast coast of China with the East China Sea lying to the east. The resident population of the province was 54.77 million at the end of 2012. We selected five cities/regions as representative of the province: Hangzhou, Xiaoshan, Jiande, Wenzhou and Lishui. Each of these cities or regions has only one Blood Service, except Wenzhou, which has one blood station and four Blood Banks. The data for Wenzhou come from all the Blood Services in the region. Hangzhou city, the capital of Zhejiang Province, is the province's economic, cultural, scientific and educational centre. Xiaoshan and Jiande are two districts of Hangzhou. They have their own Blood Banks, but the blood testing was done in Hanzhou. Wenzhou is a prefecture-level region in the south-east of Zhejiang Province, and Lishui is a prefecture-level region in the south-west of Zhejiang Province. The regions of Jiande and Lishui are less economically developed than Hangzhou, Xiaoshan and Wenzhou, and there are more farmers and fewer migrant people living in these two regions.
HBsAg: hepatitis B virus surface antigen; HCV: hepatitis C virus; HIV: human immunodeficiency virus; TP: Treponema pallidum; HBV: hepatitis B virus.
Blood Transfus 2015; 13; 401-10 DOI 10.2450/2015.0271-14 402 All rights reserved - For personal use only No other uses without permission
Prevalence and trends of TTI among volunteer blood donors
Statistical analysis Statistical analyses were conducted using SPSS 13.0 statistics software. The chi-square test was applied to assess associations between categorical variants. The chi-square test for trends was used to analyse the differences in seroprevalence of TTI markers among different demographic groups. A p-value
M
TI S
er v
iz i
Sr l
Background. The high prevalence of hepatitis B and C viruses (HBV and HCV), paralleling the growing epidemic of human immunodeficiency virus (HIV) and Treponema pallidum (TP) infections in the general population, poses a great threat to blood safety in China. This study investigated the prevalence of serological markers for causative agents of transfusion-transmissible infections (TTI), i.e. HBV, HCV, HIV and TP, among volunteer blood donors in five cities/regions of Zhejiang Province, China. Material and methods. We investigated whole blood and apheresis donations collected at the Blood Services in five cities/regions in Zhejiang Province between January 1, 2006 and December 31, 2012. Two rounds of serological testing were performed for HBsAg, anti-HCV, anti-HIV1/2 and anti-TP using different kits. The rates of serological positivity were calculated and further analysis was performed to examine the association between donors' characteristics and seroprevalence. Results. Of the 1,615,120 donations, approximately 40% came from first-time donors and 60% from repeat donors. The overall seroprevalence rates of HBV, HCV, HIV and TP were 0.51%, 0.25%, 0.15% and 0.52%, respectively. The overall prevalences of HCV and HIV remained relatively steady, whereas the prevalence of TP increased sharply after 2010. However, the prevalence of TTI agents varied among volunteer blood donors in different cities/regions and demographic groups. Discussion. We collected data on the seroprevalence of TTI agents among volunteer blood donors. Although the risk of TTI is low in China compared to that in some developing countries, sensitive screening methods and recruitment of regular donors are still very important for blood safety and availability.
Introduction
SI
Keywords: transfusion-transmissible infection, blood donor, seroprevalence.
©
Despite significant progress made over the last few decades in the prevention of transfusion-transmissible infections (TTI) through blood transfusion, transmission of pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Treponema pallidum (TP) via transfusion still poses a great threat to blood safety. In the global view, the risk of TTI has been drastically reduced by the introduction of routine donor laboratory screening for blood-borne pathogens and by volunteer donations1,2. As a consequence of continuous implementation and improvement of more sensitive serological methods and nucleic acid amplification tests (NAT), in the European Union and the United States the residual risk of HIV and HCV among all allogeneic donations is currently below 1 per 1 million donations, and that of HBV is close to 1 per 300,000 donations3,4. In another study, estimates of residual risk among repeat apheresis donors in the United
States between 2007 and 2008 were 1:1.0 million for HIV, 1:3.2 million for HCV, and 1:200,000 for HBV5. Furthermore, one recent study in the United States showed that with the addition of minipool-NAT, and resulting 8.8-day window-period reduction, residual risks for HBV decreased from 1:765,000 to 1:1,006,0006. In China and other developing countries, the risks of TTI are higher than those in above-mentioned developed nations7-10. With the rapid growth of the Chinese economy in the last 30 years, the blood transfusion services in China have experienced great transformation and development. By the end of 2012, there were 531 Blood Centres/Banks in China, organised in three levels: provincial, regional and county Blood Services (according to the Chinese Health Statistical Digest, 2013-2014 issued by the National Health and Family Planning Commission of People's Republic of China: http://www.nhfpc.gov.cn/ewebeditor/uploadf ile/2014/04/20140430131845405.pdf, last accessed on 01/09/2014). Since the Blood Donation Law came into
Blood Transfus 2015; 13; 401-10 DOI 10.2450/2015.0271-14 © SIMTI Servizi Srl
401 All rights reserved - For personal use only No other uses without permission
Zheng X et al
iz i
Sr l
Our study population consisted of all whole blood and apheresis donors in the five cities/ regions from January 2006 through December 2012. All the candidate donors underwent pre-donation screening. The whole process included a health history questionnaire, a brief physical examination and rapid predonation testing. If donors reported in questionnaire that they had been diagnosed as having HIV infection, syphilis, or any other sexually transmitted disease or viral hepatitis, they were permanently deferred. Next, the donors had to pass a physical examination regarding body weight and blood pressure. Rapid pre-donation testing included haemoglobin level, hepatitis B virus surface antigen (HBsAg), alanine aminotransferase level and determination of ABO blood group. Potential donors with a low haemoglobin level (lower than 120 g/L in males; in females, lower than 110 g/L before June 2012 and lower than 115 g/L since June 2012), abnormal alanine aminotransferase or positive HBsAg results were temporarily deferred. All successful donations then underwent two rounds of routine serological testing for HBsAg, anti-HCV, antiHIV1/2 and anti-TP by two different reagents according to the manufacturers' instructions; both imported and domestic testing kits, approved and licensed by the Chinese State Food and Drug Administration, were used (listed in Table I). We used a dual screening strategy to test donations. If the test results from either assay in the strategy were reactive, the sample was judged positive, the donation was discarded and the donor was permanently deferred. We extracted all data
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Materials and methods
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er v
effect in 1998, many changes have been made in the field of blood banking in China and blood collection has been successfully transformed from paid and family member donations to voluntary donations. Compared to 1998, when paid donations or donations from family members made up 80% of its blood supplies, China has achieved 98.5% voluntary donations in just 10 years (http://www. who.int/mediacentre/news/releases/2008/pr18/en/, last accessed on 01/09/2014). Currently, the blood donation rate is only 9‰ of the whole population in China, which is much lower than the desired rate indicated by the World Health Organisation (WHO): 10-30‰. Although the volume of blood collected has increased dramatically, the increase in the blood supply has not kept pace with the increasing clinical demand for blood in China. Furthermore, besides the problem of blood availability, there are great challenges in ensuring blood safety. The high prevalences of HBV and HCV, paralleling the growing epidemics of HIV and TP in the general Chinese population, are at the basis of these challenges. While there has been some research focusing on the prevalence of these infectious diseases in the general Chinese population, epidemiological data on the seroprevalence of TTI agents among Chinese volunteer blood donors are still limited despite recent publications by Wang et al9,10. In this study, we investigated the seroprevalence of transfusion-transmissible pathogenic agents including HBV, HCV, HIV and TP among blood donors from 2006 to 2012 in Zhejiang Province, which is one of the most prosperous areas in China.
Table I - HBsAg, anti-HCV, anti-HIV1/2 and anti-TP reagents used for screening donors. Kit name
Company
Diagnostic kit for HBV surface antigen (ELISA)
InTec Products, Inc. (Xiamen, China); Ke-Hua BIO-Engineering Co., Ltd. (Shanghai, China); BioMérieux Clinical Diagnostics (Shanghai, China); Murex Biotech Limited (Dartford, UK)
Diagnostic kit for antibody to HCV (ELISA)
InTec Products, Inc. (Xiamen, China); Ke-Hua BIO-Engineering Co., Ltd. (Shanghai, China); Ortho-Clinical Diagnostics, Inc. (New Jersey, USA)
Diagnostic kit for antibody to HIV-1/2 (sandwich ELISA)
Livzon Diagnostics Inc. (Zhuhai, China); BioMérieux Clinical Diagnostics (Shanghai, China); Bio-Rad (Marnes-la-Coquette, France)
Diagnostic kit for antibody to Treponema pallidum (ELISA)
InTec Products, Inc. (Xiamen, China); Wan-Tai Biological Pharmacy Enterprise Co., Ltd. (Beijing, China)
©
SI
Participants and study procedure Zhejiang Province is located in the southern part of the Yangtze River Delta on the southeast coast of China with the East China Sea lying to the east. The resident population of the province was 54.77 million at the end of 2012. We selected five cities/regions as representative of the province: Hangzhou, Xiaoshan, Jiande, Wenzhou and Lishui. Each of these cities or regions has only one Blood Service, except Wenzhou, which has one blood station and four Blood Banks. The data for Wenzhou come from all the Blood Services in the region. Hangzhou city, the capital of Zhejiang Province, is the province's economic, cultural, scientific and educational centre. Xiaoshan and Jiande are two districts of Hangzhou. They have their own Blood Banks, but the blood testing was done in Hanzhou. Wenzhou is a prefecture-level region in the south-east of Zhejiang Province, and Lishui is a prefecture-level region in the south-west of Zhejiang Province. The regions of Jiande and Lishui are less economically developed than Hangzhou, Xiaoshan and Wenzhou, and there are more farmers and fewer migrant people living in these two regions.
HBsAg: hepatitis B virus surface antigen; HCV: hepatitis C virus; HIV: human immunodeficiency virus; TP: Treponema pallidum; HBV: hepatitis B virus.
Blood Transfus 2015; 13; 401-10 DOI 10.2450/2015.0271-14 402 All rights reserved - For personal use only No other uses without permission
Prevalence and trends of TTI among volunteer blood donors
Statistical analysis Statistical analyses were conducted using SPSS 13.0 statistics software. The chi-square test was applied to assess associations between categorical variants. The chi-square test for trends was used to analyse the differences in seroprevalence of TTI markers among different demographic groups. A p-value
