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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 2  |  Issue : 1  |  Page : 24-28

A study of centralized individual donor nucleic acid testing for transfusion transmitted infections to improve blood safety in Karnataka, India


1 Department of Transfusion Medicine, Bangalore Medical Services Trust, Bengaluru, Karnataka, India
2 Stem Cell Registry India, Rotary Bangalore TTK Blood Bank, Bangalore Medical Services Trust, Bengaluru, Karnataka, India

Date of Web Publication22-Mar-2017

Correspondence Address:
Ankit Mathur
Department of Transfusion Medicine, Bangalore Medical Services Trust, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_8_17

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  Abstract 

Introduction: Karnataka state has a total of 176 blood banks, with a total collection of around 650,000 units annually. From January 2014, all units under the Department of Health and Family Welfare services are tested at NAT Lab established at the Central facility and from September 2014, standalone Regional Blood Transfusion Centre was included in the State Government project. Aim and Objective: The aim of the study is to analyze the nucleic acid testing (NAT) for our donor population and demonstrate consolidation of blood transfusion service through a centralized testing center for NAT and also to assess safety benefits of implementing individual donor NAT (IDNAT). Materials and Methods: We collect nearly 40,000 units annually from voluntary donors with 30% repeat donations. The donors undergo strict predonation counseling, donor questionnaire, and medical examination. The units collected are tested for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) by ECI using VItros 3600. All the units are tested by NAT at Central NAT Lab, screened by Procleix® Panther System by Grifols. Results: From September 2014 to March 2016, total 50,903 samples tested for NAT. Of 50,903 samples, 588 samples (1.15%) were reactive by Chemiluminescence including 265 for HBV, 188 for HCV, and 135 for HIV. Total NAT reactive samples were 254, out of this 11 reactive for HIV-1 (0.02%), 2 reactive for HCV (0.003%), 235 (0.46%) reactive for HBV. There was one HIV and 10 HBV infection cases that were not detected by serology but reactive by NAT. The yield detected is 0.021% or one in 5000. Conclusion: The IDNAT project has helped in preventing window period infections thus reducing the treatment cost and burden on healthcare. It has added benefits in blood safety and should be considered along with the basic quality assured blood transfusion system such as volunteer base for blood donation, provision of donor self-deferral, donor notification, and quality assured sensitive serological methods.

Keywords: Chemiluminescence test, nucleic acid testing, window period


How to cite this article:
Mathur A, Dontula S, Jagannathan L. A study of centralized individual donor nucleic acid testing for transfusion transmitted infections to improve blood safety in Karnataka, India. Glob J Transfus Med 2017;2:24-8

How to cite this URL:
Mathur A, Dontula S, Jagannathan L. A study of centralized individual donor nucleic acid testing for transfusion transmitted infections to improve blood safety in Karnataka, India. Glob J Transfus Med [serial online] 2017 [cited 2017 Jun 26];2:24-8. Available from: http://www.gjtmonline.com/text.asp?2017/2/1/24/202722


  Introduction Top


The key to recruiting and retaining safe blood donors is the understanding of infectious markers in the general population to identify low-risk donor populations coupled with an effective donor education, motivation, and recruitment strategy. Voluntary nonremunerated blood donations in India rose from 54.4% in 2006 to 74.1% in January 2010.[1]

Nucleic acid testing (NAT) is a molecular technique for screening blood donations to reduce the risk of transfusion-transmitted infections (TTIs) in the recipients, thus providing an additional layer of blood safety. It was introduced in the developed countries in the late 1990s and early 2000s, and currently around 33 countries in the world have implemented NAT for human immunodeficiency virus (HIV) and around 27 countries for hepatitis B virus (HBV).[2] NAT technique is highly sensitive and specific for viral nucleic acids. It is based on amplification of targeted regions of viral ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) and detects them earlier than the other screening methods thus, narrowing the window period of HIV, HBV, and hepatitis C virus (HCV) infections.

The blood samples can be pooled together in a batch of 6 or 8 before testing to screen a large number of donations with few tests (mini-pool NAT [MPNAT]), or the tests can be run on every individual sample (individual donor NAT [IDNAT]). It has been debated in various studies whether pooling of samples results in decreased sensitivity of detection as the volume of the individual sample gets lesser in a pool. Therefore, greater the number of samples in a pool, lesser is the sensitivity of detection of the test. Furthermore, the replication rate of HBV is very low, with a mean doubling time of 2.6 days and the viral load is also very low during the window phase.[3],[4]

The introduction of NAT for screening pooled or individual donations has led to improved blood safety. The size of MPNAT is considered critical for identification of infected donors, during the preseroconversion phase of infection. A very small size of the pool helps greater reduction in the serological window phase.[5] However, the feasibility of NAT for a developing country like India or its application to Indian blood transfusion service (BTS) has been a topic of debate.

The risk of viral infection is lower today than ever before, due to improvements in donor screening and testing practices. NAT has lowered this risk even further in few centers where this has been adopted. However, this additional benefit comes at an additional cost to the health-care system.[6]

Most reports from high prevalence low resource countries showed a yield as high as 1/2800 for HBV and 1/3100 blood donations for HCV with NAT testing.[7]

Confidence in results of TTIs in a blood bank is of critical importance. Although enzyme-linked immunosorbent assay blood screening technology relies on the detection of serological markers, these markers may not appear in the blood until up to 3 months after an infection, leaving a “window period” in which a risk of transfusion-transmitted infection is increased. NAT assay reduces this window period by detecting the presence of the viral RNA or DNA directly. Depending on the sensitivity of the test, implementation of HBV NAT has the potential to reduce the risk of infection to levels similar to those for HIV and HCV.

In India, mandatory blood screening for HBV, HIV, and HCV is done by serological tests for hepatitis B surface antigen and antibodies to HIV 1/2 and HCV. The screened seronegative donations are still at risk for TTIs and thus, need for a sensitive screening test arises to decrease this residual risk. This has been reduced significantly over the last two to three decades in western countries where NAT has been implemented. NAT testing has commenced in few centers in India, but it is not a mandatory screening test for TTIs as per Drug and Cosmetics Act, 1940.[8] Major barriers to implementing routine NAT testing in India is its high cost and lack of technical expertise in most of the blood centers.[9]

The government of Karnataka becomes the first State Government to implement IDNAT in 2011. Karnataka state has a total of 176 blood banks, with a total collection of around 650,000 units annually. From January 2014, all units under the Department of Health and Family Welfare services are tested at NAT Lab established at Central facility and from September 2014, standalone Regional Blood Transfusion Centre (RBTC) was included in the State Government project.

Aim and objective

  • To analyze the NAT for our donor population
  • To demonstrate consolidation of BTS through a centralized testing center for NAT and also to assess safety benefits of implementing IDNAT.



  Materials and Methods Top


RBTC collects nearly 40,000 units annually from voluntary donors with 30% repeat donations. The donors undergo strict predonation counseling, donor questionnaire, and medical examination. The units collected are tested for HIV, HBV, and HCV by Enhanced Chemiluminescence test by Ortho Clinical Diagnostics using VItros 3600. This is used as main serological screening test for all three viral markers. The testing for syphilis was done by Rapid Plasma Reagin test and Malaria by peripheral smear.

From September 2014, all the units were tested by NAT at Central NAT Lab, screened by using Procleix ® Ultrio Elite Assay kits in the Grifols Procleix Panther System. The NAT test was added as a supplementary test along with routine serology.


  Results Top


From September 2014 to March 2016, total 50,903 samples tested for NAT. Of 50,903 samples, 588 samples (1.15%) were reactive by Chemiluminescence test including 265 for HBV, 188 for HCV, and 135 for HIV [Table 1]. All the samples were sent for NAT testing. Out of 50,903, total NAT reactive samples were 254, out of this 11 reactive for HIV-1 (0.02%), 2 reactive for HCV (0.003%), 235 (0.46%) reactive for HBV. There was one HIV and 10 HBV infection cases that were not detected by serology but reactive by NAT as shown in [Figure 1] and [Figure 2]. The yield detected is 0.021% or one in 5000. This yield was found lower than other blood banks participating in the project where it was detected one in 300–500 donations.
Table 1: Total number of sero reactive and NAT reactive samples

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Figure 1: Sero reactive, NAT reactive and NAT yield numbers

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Figure 2: Sero reactive, NAT reactive and NAT yield numbers for HBV, HCV and HIV

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There are many samples which were reactive with serology but nonreactive with NAT. These could be false positive due to the high sensitivity of chemiluminescence technology. Further investigation has to be done to conclude it.


  Discussion Top


A safe, effective BTS is an essential component in the provision of an adequate health-care service. It is the responsibility of the state to ensure safe blood by improvement of the service through accommodating modern facilities and techniques, establishment of infrastructure, development of workforce, and policies. WHO recommends centralized/regionalized testing as one of the policies to be adopted to improve blood safety.

NAT testing is more sensitive than conventional tests. While the conventional methods depend on antibodies to produce a positive result, NAT is based on the presence of viral genetic material NAT can detect the low levels of viral genetic material present in the body. This happens before the body begins producing antibodies in response to a virus, giving the ability to detect a disease at an earlier stage.

In India, screening for HIV, hepatitis B, and hepatitis C is based on serological testing with the recent introduction of NAT testing in few centers. Even after implementing the more sensitive, newest generation of serological tests, a considerable residual risk of infection remains.[10] Most populations in resource-limited regions suffer from a high prevalence rate of TTIs and are expected to have more frequent incident cases, as well as more occult carriers. Countries with a high prevalence and incidence of infection are likely to yield a significant number of window period donations. Consequently, NAT screening of TTIs in these populations would be expected to identify more yield cases as compared to the developed world and thus to be more cost effective.

In one study from North India,[1] the HBV NAT yield was 1:2972 donations which is much higher than in studies done in Western Europe and the USA, where the reported prevalence is around 1:600,000–1:350,000 donations and in developing countries such as South Africa, Thailand, Kuwait, and Malaysia where the HBV NAT yield was 1:52,303, 1:4868, 1:24,275, and 1:3616 donations, respectively, as compared to high prevalence developing countries such as 1:232 in Ghana, 1:2609 in Egypt, 1:501 in Lebanon, 1:125 in Iran, 1:69 in Mozambique, 1:193 in Pakistan, 1:865 in Mexico, 1:81 in Mongolia, and 1:1430 in China.

Another study from South India shows a NAT yield of 1:53,260 for HIV and 1:26,630 for HBV. The lower NAT yield compared to Jain et al. and Makroo et al.[1],[10] study and Jain et al.'s study is probably on account of the lower seroreactivity rate. The stringent donor screening measures may also have contributed to lower seroreactivity and consequently lower NAT yield in our study.[1],[10],[11]

The utility of NAT (NAT yield) will vary based on the donor population, the type of serological test employed, the nature of the kit employed and also based on the sensitivity of NAT test employed. Patterns of infections among blood donors in our country also vary widely, and TTIs continue to be a threat to safe transfusion practices.[12] TTIs is still a major concern to patients, physicians, and policymakers who seek a risk-free blood supply. Results of NAT testing vary significantly based on these factors.

While studies in developing countries have shown high NAT yields,[1],[10] as high as 1/2800 for HBV and 1/3100 blood donations for HCV, other studies in developed countries of Central Europe [13] have shown that yield of NAT using sensitive MPNAT assays is less than expected. After screening 3.6 million donations for HCV and HIV, the NAT yield was found to be 1:600,000 for HCV-RNA and 1 in 1.8 million for HIV-RNA. Another large study in the USA [14] screened 66 million donations by NAT over a 10-year period beginning in 1999 and identified additional 32 HIV cases (NAT yield for HIV 1:2 million) and another 244 HCV cases (NAT yield for HCV 1:270,000).

In India, blood centers are gradually introducing NAT to provide safe blood to their patients. First multicentric study was done by Makroo et al.[10] where a total of 12,224 samples along with their serological results were obtained from eight blood banks in India and were tested individually manually by Procleix Ultrio assay for HIV 1, HCV, and HBV. They observed eight NAT yield cases. This high yield of NAT is due to the high prevalence of TTIs in India, further highlighting the need for NAT in India. In another study from a tertiary care center from North India IDNAT results were compared to serological method for 73,898 samples, 1.49% were reactive by NAT, HIV-1 (0.09%), HCV (0.25%), 1.05% were reactive for HBV only, and around 0.08% were HBV-HCV coinfections with a combined yield of 1 in 610 donations (total 121 NAT yields).[15]

NAT is a highly sensitive and advanced technique which has reduced the window period of HBV to 10.34 days, HCV to 1.34 days, and HIV to 2.93 days [16] but it is highly technically demanding, involving issues of high costs, dedicated infrastructure facility, equipment, consumables, and technical expertise. The need for NAT depends on the prevalence and incidence rate of infections in blood donor population, available resources and the evidence of benefit added when combined with serology tests. Hence, the decision of starting NAT should be considered when basic quality assured blood transfusion system is already in place such as volunteer base for blood donation, provision of donor self-deferral, donor notification, and counseling along with quality assured sensitive serological methods for testing TTIs.


  Conclusion Top


  • The NAT yield detected in the study was 1 in 5000 which is lower than most of the studies found in India. The implementation of NAT improved blood safety and able to detect window period infection
  • It has added benefits in blood safety and should be considered along with the basic quality assured blood transfusion system such as volunteer base for blood donation, provision of donor self-deferral, donor notification, and quality assured sensitive serological methods
  • The NAT consolidation project has helped in reducing window period infections thus reducing the treatment cost and burden on healthcare. The centralization of facility helped in maintaining the quality standards of testing as well in lowering the cost to make it affordable
  • The centralization of facility helps to bring uniformity in quality control, but such centralized laboratories should go in for mandatory accreditation to assure community confidence. The centralized testing despite economies of scale has not brought down the cost per test significantly. However, the cost of NAT is being subsidized by the state government to make safe blood more affordable.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Jain R, Aggarwal P, Gupta GN. Need for nucleic acid testing in countries with high prevalence of transfusion-transmitted infections. ISRN Hematol 2012;2012:718671.  Back to cited text no. 1
    
2.
Roth WK, Busch MP, Schuller A, Ismay S, Cheng A, Seed CR, et al. International survey on NAT testing of blood donations: Expanding implementation and yield from 1999 to 2009. Vox Sang 2012;102:82-90.  Back to cited text no. 2
    
3.
Najioullah F, Barlet V, Renaudier P, Guitton C, Crova P, Guérin JC, et al. Failure and success of HIV tests for the prevention of HIV-1 transmission by blood and tissue donations. J Med Virol 2004;73:347-9.  Back to cited text no. 3
    
4.
Yang MH, Li L, Hung YS, Hung CS, Allain JP, Lin KS, et al. The efficacy of individual-donation and minipool testing to detect low-level hepatitis B virus DNA in Taiwan. Transfusion 2010;50:65-74.  Back to cited text no. 4
    
5.
Palla P, Vatteroni ML, Vacri L, Maggi F, Baicchi U. HIV-1 NAT minipool during the pre-seroconversion window period: Detection of a repeat blood donor. Vox Sang 2006;90:59-62.  Back to cited text no. 5
    
6.
Jackson BR, Busch MP, Stramer SL, AuBuchon JP. The cost-effectiveness of NAT for HIV, HCV, and HBV in whole-blood donations. Transfusion 2003;43:721-9.  Back to cited text no. 6
    
7.
El Ekiaby M, Lelie N, Allain JP. Nucleic acid testing (NAT) in high prevalence-low resource settings. Biologicals 2010;38:59-64.  Back to cited text no. 7
    
8.
Part XIIB. Department of Health Schedule F. The Drugs and Cosmetics Act, 1940 and the Drugs and Cosmetics Rules, 1945, as Amended Up To 30th June, 2005. Government of India. Ministry of Health and Family Welfare; 2005. p. 326. Available from: http://www.cdsco.nic.in/DrugsandCosmeticAct.pdf. [Last accessed on 2013 Apr 04].  Back to cited text no. 8
    
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Hans R, Marwaha N. Nucleic acid testing-benefits and constraints. Asian J Transfus Sci 2014;8:2-3.  Back to cited text no. 9
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10.
Makroo RN, Choudhury N, Jagannathan L, Parihar-Malhotra M, Raina V, Chaudhary RK, et al. Multicenter evaluation of individual donor nucleic acid testing (NAT) for simultaneous detection of human immunodeficiency virus-1 & hepatitis B & C viruses in Indian blood donors. Indian J Med Res 2008;127:140-7.  Back to cited text no. 10
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11.
Chandrashekar S. Half a decade of mini-pool nucleic acid testing: Cost-effective way for improving blood safety in India. Asian J Transfus Sci 2014;8:35-8.  Back to cited text no. 11
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12.
Kaur G, Basu S, Kaur R, Kaur P, Garg S. Patterns of infections among blood donors in a tertiary care centre: A retrospective study. Natl Med J India 2010;23:147-9.  Back to cited text no. 12
    
13.
Roth WK, Weber M, Buhr S, Drosten C, Weichert W, Sireis W, et al. Yield of HCV and HIV-1 NAT after screening of 3.6 million blood donations in Central Europe. Transfusion 2002;42:862-8.  Back to cited text no. 13
    
14.
Zou S, Dorsey KA, Notari EP, Foster GA, Krysztof DE, Musavi F, et al. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 2010;50:1495-504.  Back to cited text no. 14
    
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Agarwal N, Chatterjee K, Coshic P, Borgohain M. Nucleic acid testing for blood banks: An experience from a tertiary care centre in New Delhi, India. Transfus Apher Sci 2013;49:482-4.  Back to cited text no. 15
    
16.
Weusten J, Vermeulen M, van Drimmelen H, Lelie N. Refinement of a viral transmission risk model for blood donations in seroconversion window phase screened by nucleic acid testing in different pool sizes and repeat test algorithms. Transfusion 2011;51:203-15.  Back to cited text no. 16
    


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