BABUBLAL MANGALJIBHAI THAKKAR....Applicant(s)V/SDIRECTOR C/WPPIL/156/2012 CAV JUDGEMNT IN THE HIGH COURT OF GUJARAT AT AHMEDABAD WRIT PETITION (PIL) NO. 156 of 2012 With CIVIL APPLICATION NO. 10354 of 2012 In WRIT PETITION (PIL) NO. 156 of 2012 with CIVIL APPLICATION No. 2767 of 2012 In WRIT PETITION (PIL) No. 151 of 2011 with CIVIL APPLICATION No. 9282 of 2012 In CIVIL APPLICATION No. 2767 of 2012 FOR APPROVAL AND SIGNATURE: HONOURABLE THE CHIEF JUSTICE MR. BHASKAR BHATTACHARYA and HONOURABLE MR.JUSTICE J.B.PARDIWALA ================================================================1
Whether Reporters of Local Papers may be allowed to see the judgment ?2
To be referred to the Reporter or not ?3
Whether their Lordships wish to see the fair copy of the judgment ?4
Whether this case involves a substantial question of law as to the interpretation of the Constitution of India, 1950 or any order made thereunder ?5
Whether it is to be circulated to the civil judge ?
================================================================ BABUBLAL MANGALJIBHAI THAKKAR....Applicant(s) Versus DIRECTOR &
2....Opponent(s) ================================================================ Appearance:
DELETED for the Applicant(s) No. 1 MR.
SHALIN MEHTA, LD. SENIOR COUNSEL APPEARING AS AMICUS CURIAE.
P.K. JANI, LD. GOVERNMENT PLEADER WITH MRS. KRINA CALLA, LD. ASSISTANT GOVERNMENT PLEADER FOR RESPONDENT NOS. 1-2 MR AMIT PANCHAL, LD. COUNSEL with MR MK VAKHARIA, LD. ADVOCATE for respondent no.3 MR.
P.S. CHAMPANERI, LD. ASSISTANT SOLICITOR GENERAL OF INDIA for Resp. No.4 ================================================================ CORAM:
HONOURABLE THE CHIEF JUSTICE MR. BHASKAR BHATTACHARYA and HONOURABLE MR.JUSTICE J.B.PARDIWALA Date :22/08/2013 CAV JUDGEMENT (PER : HONOURABLE MR.JUSTICE J.B.PARDIWALA) Pursuant to our order dated 8th November, 2012, by which we had directed the respondent No.3, Ministry of Health and Family Welfare Department, Government of India, to constitute a body of experts in the subject to examine the feasibility of making PCR tests mandatory at all licensed blood banks across the country, such Committee was constituted and has placed its report for our consideration. In our order dated 8th November, 2012, we observed as under:-
"10. Taking into consideration the complex nature of the issue with which we are dealing, we have to be mindful of the principle that judicial review of a policy evolved by the Government is limited. On matters affecting policy and requiring technical expertise, the court would leave the matter for decision of those who are qualified to address the issues.
15.2 We have no doubt in our mind after going through the materials on record that PCR Test is a superior test compared to ELISA Test. The importance of PCR Test lies in its capacity to detect the virus during the Window Period. According to the study of the medical science, the length of time following the infection of an individual to develop detectable antibodies is about three months after the infection, this is called the Window Period . Take a case where the ELISA Test fails to detect HIV virus during the Window Period and on the strength of such negative report if such blood containing HIV virus is transfused to a person, he would easily get affected by the HIV virus. It is at that stage, perhaps, by way of abundant caution that the PCR Test could also be undertaken to rule out the presence of the HIV virus in the blood during the window period.
15.3 The materials on record also suggest that testing kits, so far as ELISA Test is concerned, are easily available as there are many manufacturers in the market, whereas the testing kits for PCR Test are not being manufactured on large scale and the cost factor is also compared to the ELISA Test much higher. However, we would like to make one aspect very clear that when we are dealing with the subject of life of a citizen, the cost should not be a factor so far as the Government is concerned. It is the duty of the Government to protect the life of its citizens and it would not lie in the mouth of any Government to say that because of cost factor, the PCR Test is to be ruled out. Life is priceless. However, we have also noticed that the PCR Test takes around 16 hours to give necessary results, whereas the ELISA Test takes around 1.5 hours. In a given case, when there is an urgent need of blood transfusion, then the time factor would also play a crucial role. It appears to us that there are positive aspects as well as negative aspects of the PCR Test and as pointed out by Mr.Jani, the learned Government Pleader, the Act also prescribes the ELISA Test.
15.4 This is a matter of policy, and therefore, this Court sitting in a public interest jurisdiction should not issue directions to the State Government or the Union of India to frame a particular legislation, e.g. introducing the PCR Test.
15.5 We are, therefore, of the view that this issue needs to be looked into very extensively by a body of experts in the field. When the Central Government has already declared way back in the year 2006, introduction of DNA Polymerase Chain Reaction (PCR) Test, a dry blood sampling method of testing for paediatrics AIDS, then in such circumstances, the Central Government, after seeking opinion from a body of experts, should also consider implementation and execution of the same in its true perspective.
15.6 We, therefore, direct the respondent No.3-Ministry of Health and Family Welfare Department, Government of India, to constitute a body of experts in the subject to examine as to what extent the PCR Test could be made mandatory at all licensed blood banks across the country. We direct the respondent-Union of India to constitute such committee within a period of two months from today. The Committee constituted shall consider the issues raised in this writ-application and place its report before this Court within a period of three months thereafter."
2. We have perused the report. Annexure I to the report provides for the following List of Members of the Expert Group.
Dr Sunil D.
Khaparde, Deputy Director General, Blood Safety, Department of AIDS Control, Ministry of Hezlth and Family Welfare.
1. Dr. Zarin Bharucha, Transfusion Medicine Expert,
2. Dr. Bharat Singh, Director, State Blood Transfusion Council, Delhi;
3. Dr. J.P.
Prasad, Scientist, National Institute of Biologicals,
4. Shri Venkateshwarlu, Deputy Drug Controller, CDSCO,
5. Dr. Lalit Dar, Professor and Incharge, Virology Section, Department of Microbiology, AIIMS,
6. Dr. Ramesh Paranjape, Director, NARI,
7. Dr. Shiv Lal, Public Health Expert,
8. Dr. Rajendra Chaudhry, Head of Department, Transfusion Medicine, SGPGI,
9. Dr. Arun Risbud, Scientist, NARI,
Dr. Shobini Rajan, Assistant Director General, Blook Safety, Department of AIDS Control, Ministry of Health and Family Welfare,
3. Annexure II contains the information regarding Global and National scenario with references. They are reproduced below:-
1. The Cochrane meta-analysis review article states that the PCR, nucleic acid sequence-based amplification (NASBA) and branched DNA (bDNA) methods provide a large increase in the sensitivity towards early infection, thereby increasing the safety of blood supplies.
a. Several studies have confirmed the accuracy of current methods of HIV testing in the USA, reporting false-positive rates of 0.0004% to 0.0007% and false-negative rates of 0.003% in the general population (Burke 1988; Busch 1991; Farzadegan 1993; Kleinman 1998; MacDonald 1989; Urnovitz 1997;
Van de Perre 1991).
b. Fourth-generation combination EIAs, widely used in other industrialized countries, identifies HIV infection even earlier because they detect both the HIV antibody and p24 antigen (Branson 2007). These newer EIAs are able to detect HIV antibodies within two to six weeks after infection.
c. The NAAT tests appear reasonable for detection and early diagnosis of patients believed to be infected with HIV-1 and HIV-2 because infected people can have a positive NAAT after the first week of infection, while the ELISA is only positive from the third or fourth week (this gap period is called the window period).
2. The Scottish National Blood Transfusion Service (SNBTS) implemented NAAT in 1999.
a. The HCV and HIV NAAT assays have 95% detection levels of 7-25 IU/ml and 39-8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1-9 million) and one HIV (1 in 0-77 million) window donation have been detected in 5 and 2 years, respectively, of NAAT.
b. Clearly NAAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAAT.
3. The review article on TTIs showed that The implementation of viral NAAT testing has greatly helped to reduce the residual risk of viral transmission during the 'window period' by reducing the time for effective detection from 22 days (with solely serological testing) to 11 days for HIV and from 70 to 10 days for HCV. As a consequence, the estimated risk for HIV transmission to date is between 0.14 - 1.1 and for HCV between 0.10 - 2.33 per million units transfused.
The table showing Relative Risk of the most frequent TTI in Donated blood at USA and Europe.
Risk factor/infectious agent Risk of TTI in blood products released U.S.
Europe Virus HIV 1 in 2,135,000 1 in 909,000 5,500,000 HCV 1 in 1,930,000 1 in 2,00,000 -4,400,000 HBV 1 in 277,000 1 in 72,000 1,100,000* Parasites Malaria 1 in 1,000,000 -5,000,000 b. As
shown in a recent study assessing the risks of transfusion-mediated HIV and HCV infections between 1999 and 2003, the benefits of NAAT testing over antibody testing were confirmed by showing that one out of 230,000 donations tested positive for HCV RNA but not for anti-HCV antibodies. For HIV, with an apparently shorter window period, one out of 3.1 million donations was RNA positive but antibody negative. However, the observed NAAT detection rates and its relative benefits can vary widely between sites.
For instance, in Europe only 54 anti-HCV antibody negative, HCV RNA positive samples were identified among 58 million donations tested (NAAT yield:
0.93 NAAT reactive sample per million antibody negative donations) compared to North America (NAAT yield: 3.92/million donations) or the Pacific area (NAAT yield: 2.37/million donations).
c. HBV surface antigen (HbsAg), the main screening target, is routinely included in the donor screening, but fails to detect the presence of HBV during the 'window period'. A number of countries have also added the testing for antibodies directed against the HBV core protein (anti-HBc) to the standard screening in an attempt to detect chronic virus carriers with low-level viremia who may not have detectable HBsAg levels. Today, the residual risk of TT HBV infection varies between 0.75 per million blood donations in Australia, 3.6 - 8.5 in the USA and Canada, 0,91 - 8.7 in Northern Europe, 7.5 - 13.9 in Southern Europe up to 200 per million donations in Hong Kong, largely reflecting the global epidemiology of HBV. However, there is no evidence, so far, that pooled testing with HBV NAAT is superior to the most sensitive tests for HBsAg.
4. The France study - Nucleic acid testing has been routinely performed in all blood donations in France since July 1st 2001.
Out of 22.3 million donations over the period (2001-2009), 22 donations have been rejected because of nucleic acid testing positive for hepatitis C virus (n=ll) and human immunodeficiency virus (n=ll).
5. The CDC paper showed that the yield of nucleic acid amplification testing (NAAT) after routine screening for human immunodeficiency virus (HIV) antibody to detect acute HIV infection (AHI) may vary with different HIV-antibody assays.
a. After third-generation testing, 54 948 persons underwent NAAT; 12 AHI cases were identified, increasing HIV case detection by 1.4%. Overall, pooled NAAT after negative third-generation test results detected 26 AHI cases, increasing HIV case detection by 2.2%.
b. Pooled NAAT after third-generation testing increases HIV case detection, especially in venues of high HIV seropositivity. Therefore, targeted AHI screening using pooled NAAT after third-generation testing may be most effective, warranting a cost-benefit analysis.
The Thai study showed that the NAAT yield rates for human immunodeficiency virus Type 1 (HIV-1), hepatitis C virus(HCV), and hepatitis B virus (HBV) were 1:97,000,1:490,000, and 1:2800, respectively. Several occult HBV donors, the majority of whom were detected byboth tests, were also identified. The HIV-1 and HCV window cases were detected with both tests.
In another Thai study on Occult HBV detection using NAAT testing showed that -
Of 175 HBV NAAT-yield donors, 72 (41%)were followed. Based on the follow-up results, the majority of donors who were followed had an occult HBV infection (66.7%), followed by donors with a primary, acute infection (26.4%). The majority of donors in this latter group (20.8%) were in the window period. Three donors (4.2%), who were anti-HBs positive, had a reinfection or breakthrough infection.
8. In a study conducted at UAE, where 85% of population is non UAE and comprising of 181 nationalities ; 169,781 donations were screened with NAAAT and the results shown a.
The individual prevalence of HBV, HCV, and HIV per 100,000 donation were 234.4, 110, and 4, respectively. Calculated residual risk per million donations for HBV was decreased from 1.41 in pre-NAAT period to 0.92 in post-NAAT period. These figures were decreased for HCV and HIV from 1.73 and 0.39 to Oand 0.32, respectively.
The study recommends the parallel use of both serology and ID-NAATfor screening in blood donations.
9. In a per published by Paul-Ehrlich-Institute of Germany shown even NAAT testing can yield false negative results in some circumstances.
The paper described five cases of human immunodeficiency virus Type 1 (HIV-1) RNA-positive blood donations that escaped detection by three different CE-marked nucleic acid amplification technique(NAAT) screening assays.
Based on this experience with false-negative tests results by mono target NAAT assays, the Paul-Ehrlich-Institute is considering requesting dual-target NAAT assays for HIV-lblood donation screening in Germany.
10. In the study by Dr Bharat Singh, from Delhi, there was no discrepancy found in the results of ELISA and NAAT Screening for HIV-1 and HCV infections in the blood donors. All the ELISA reactive samples were found positive by NAAT and all ELISA non reactive were tested negative by NAAT technology. There were 11 discordant samples found in the results of ELISA and NAAT Screening for HBV infections in the blood donors. These were tested negative by ELISA and found reactive by NAAT.
a. In India, where the majority of donors are still replacement donorsl, the risk of transfusion transmitted viral infections is much higher than in countries with a 100% voluntary donor base. The prevalence of post transfusion HBV and HCV in India is between 1 to 5%1. The prevalence of HIV varies from region to region, being particularly high in western and southern parts of India b. The NAAT screening available ensures 99.99% blood safety.
11. Dr Makroo et al study from North India studies the HIV prevalence among blood donors a. This single centre study was carried out to observe the HIV-1 and HIV-
2prevalence among blood donors from north India.
b. A total of 2,04,677 people were screened for the presence of HIV infection over the 11 year period (1999 to 2009). Till 2004, a third generation ELISA kit was used. From 2005 till January 2009 all tests were done using the fourth generation ELISA kit which detected the presence of HIV-1 P24 antigen and anti-HIV antibodies. From February 2009 onwards, the kits used were Genscreen ULTRA HIV Ag-Ab Assay.
c. A total of 506 (0.247%) donors were found to be repeat reactive for HIV. Of these, 486 (96%) donors tested using the Western blot were found positive for HIV-1 infection. Twenty (4%) donors showed a negative Western blot result, none of the donors were found reactive for HIV-2 infection.
d. The prevalence of HIV was 0.249 per cent among blood donors of North India.
e. No HIV-2 case was found among the studied blood donor population indicating that it is not a threat currently.
12. In another study by Dr Makroo et al, which is multicentric study involving 8 blood banks published in 2008, has shown a. A total of 12,224 unlinked samples along with their serological results were obtained from representative eight blood banks in India and were individually manually tested by the Procleix¿ Ultrio¿Assay (Chiron Corp. Emeryville, CA) for simultaneous detection of HIV-1, HCV, and HBV.
b. Of the 12,224 samples tested, 209 (1.71%) were seroreactive.
c. One hundred thirty three samples(1.09%) were reactive by Ultrio assay, 84 samples were seroreactive but NAAT non reactive.
d. There were eight NAAT yield cases: 1 HIV, 1 HIV-HCV co-infection, and 6 HBV.
e. Our observed NAAT yield for all three viruses was 1 in 1528 (0.065%).
The authors estimate NAAT could interdict 3272 infectious donations a year among our approximate 5 million annual donations.
13. The paper of Agarwal et al which describes the analyzed the data of blood bank at AIIMS, Delhi has shown a. Out of 73,898 samples, 1104 samples (1.49%) were reactive by NAAT. out of thesell04 samples, 73 were reactive for HIV-1 (0.09%), 186 were reactive for HCV only(0.25%), 779 (1.05%) were reactive for HBV only, and around 66 (0.08%) were HBV-HCV co-infections. There was one HIV, 37 HCV, 73 HBV and 10 HBV-HCV co-infection cases that were not detected by serology but reactive on NAAT testing, with a combined yield of 1 in610 donations (total 121 NAAT yields).
b. NAAT could detect HIV, HBV and HCV cases in blood donor samples that were undetected by serological tests, c. NAAT can interdict a large number of infected unit transfusions and thus help in providing safe blood to the patients.
1. Nucleic acid amplification techniques (NAATs) for early diagnosis of HIV-1 and HIV-2 infections. Regina P El Dib1'", Mariska M.G. Leeflang2, Joseph L Mathew3, et al. Editorial Group: Cochrane HIV/AIDS Group. Published Online: 15 JUN 2011.DOI: 10.1002/14651858.CD009184. the article is based on reviewing the following data bases -:
a. The Cochrane HIV Group Specialised Register, b. DARE (Database of Abstracts of Reviews of Effects (The Cochrane Library), c. HTA database (The Cochrane Library), d. MEDLINE (1995 to present), e. EMBASE (1995 to present), f. LILACS (Literatura Latino-Americana e do Caribe emCiencias da Saude) (1995 to present), g. MEDION (The Medion database), h. ARIF (Aggressive Research Intelligence Facility) Detection of HCV and HIV-1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing.L.
M. Jarvisl,*,B. C. Dow2,A. Clelandl, et al . Article first published online: 26 AUG 2005. DOI: 10.1111/j.1423-0410.2005.00686.x Transfusion-transmitted infections.FEorian Bihl1', Damiano Castelli-, Francesco Marincola3, Roger Y Dodd- and Christian Brander1.
Journal of Transiationai Medicine 2007, 5:25 doi:10.1186/1479-5876-5-25.
Ten years of nucleic acid testing: lessons and prospects. [Article in French], Morel P. TransfusClin Biol.
2011 Apr;18(2):133-9. doi: 10.1016/j.tracli.2011.01.007. Epub 2011 Mar 11.
Detecting acute human immunodeficiency virus infection using 3 different screening immunoassays and nucleic acid amplification testing for human immunodeficiency virus RNA, 2006-2008. Patel_P, Mackeliar D, Simmons P.
Unival A, et al. Arch Intern Med.
2010 Jan ll;170(l):66-74. doi: 10.1001/archinternmed.2009.445.
One-year experience of nucleic acid technology testing forhuman immunodeficiency virus Type 1, hepatitis C virus, andhepatitis B virus in Thai blood donations.SoisaangPhikulsod, Sineenart Oota, Tha weesakTira watnapong, Occult hepatitis B virus infection in Thai blood donors.SudaLouisirirotchanakul, Sineenart Oota, KalayaneeKhuponsarb et al. Trends in prevalence, incidence, and residual risk of majortransfusion-transmissible viral infections in United ArabEmirates blood donors: impact of individual-donationnucleicacid testing, 2004 through 2009_3740 1..10. Laila Al Shaer, MaheraAbdulRahman, Thomas J. John, and All AlHashlmi.
Nucleic Acid Testing (NAAT) screening of blood donors in India: a project report Dr Bharat Singh, MD. Director, State Blood Transfusion Council, Guru TeghBahadur Hospital & University College of Medical Sciences and Government of NCT Delhi.
10. Prevalence of HIV among blood donors in a tertiary care centre of north India./?.N.
Makroo, MohitChowdhry, AakankshaBhatialv\6\av\ J Med Res 134, December 2011, pp 739-1002.
11. Multicenter evaluation of individual donor nucleic acid testing (NAAT)for simultaneous detection of human immunodeficiency virus -1 &hepatitis B & C viruses in Indian blood donors. R.N. Makroo, N. Choudhury*, L. JaganNAAThan**. Indian J Med Res 127, February 2008, pp 140-147.
12. Nucleic acid testing for blood banks: An experience froma tertiary care centre in New Delhi, India.N.
Agarwal ¿, K. Chatterjee, P. Coshic, M. Borgohain.Transfusion and Apheresis Science xxx (2013) xxx-xxx. 5th March 2013.
13. Blood screening nucleic acid amplification tests for humanimmunodeficiency virus Type 1 may require two different amplification targets. Michael Chudy, Marijke Weber-Schehl, Lutz Pichletal.
14. Screening Donated Blood for Transfusion-Transmissible lnfections. WHO, 2010.PP
4. The Committee has also given a fair idea about the types of assays which are used in India for screening of donated bloods. They are as under:-
The main types of assays which are used in India for screening of donated blood are:
1.Immunoassays (IAs) for antibodies (or antibodies plus antigen), e.g., Enzyme immunoassays (EIAs) and rapid/simple single-use assays (rapid tests) for HIV 1 and HIV 2, that permit testing of single samples as well.
2. Nucleic acid amplification technology (NAAT) assays. This technology, as applied to blood screening, detects the presence of viral nucleic acid, DNA or RNA, in donation samples. In this technology, a specific RNA/DNA segment of the virus is targeted and amplified in-vitro. The amplification step enables the detection of low levels of virus in the original sample by increasing the amount of specific target present to a level that is easily detectable. The presence of specific nucleic acid indicates the presence of the virus itself and that the donation is likely to be infectious. NAAT assays can either be performed on individual donations (ID) or on mini-pools (MP) to detect the nucleic acid of the infectious agent. In addition to NAAT assays, which target individual viral nucleic acids, multiplex NAAT screening assays have been developed which can detect DNA or RNA from multiple viruses simultaneously (WHO, 2010).
NAAT ASSAYS FOR SCREENING DONATED BLOOD NAAT assays for screening transfusion-transmitted viral infections in donated blood should detect at least infections by all the following viruses: HIV-1, HIV-2, Hepatitis B virus (HBV) and Hepatitis C virus (HCV).
The following multiplex assays, which can detect multiple viruses in individual blood donations, are currently available in India for this purpose:
Types of multiplex assays (Source: Modified from FDA, USA) s.
Trade name (s) with link to original letter and labeling Current Manufacturer Principle Infectious Agent Detected Remarks
1. COBAS Roche Multiplex HBV Detects TaqScreen MPX polymerase HCV infections Test chain reaction HIV-1 due to all (PCR) HIV-2 four viruses
2. ProcleixUltrio Assay Novartis Transcription mediated amplification (TMA) HBV, HCV, HIV-1 Does not detect HIV-2 Specificity of NAAT Definition of specificity: Specificity is defined as the ability of a test to identify correctly all those who do not have the disease that is "true negative". NAAT tests have high specificity, but tend to give faise positive results.
Sensitivity of NAAT Definition of sensitivity; Sensitivity is a statistical index of diagnostic accuracy. It has been defined as the ability of a test to identify correctly all those who have the disease that is "true positive".
NAAT tests have high sensitivity, but tend to miss immunoassay positive samples and give false negative results.
Additional Yield Additional yield definition: Yield is amount of previously unrecognized disease that is diagnosed as a result of the screening effort. It depends on sensitivity, specificity of test and prevalence of disease.
(In case of NAAT additional yield, it refers to infection that is not detected by ELISA, but detected by NAAT) In the published multicentric study (Makroo et al, 2008), the observed additional yield with NAAT for all three viruses combined was 1 in 1528 (0.065%).
Review of available national and international literature has not provided data to define what should be statistically significant acceptable norm for additional yield for NAAT.
Additional yield depends upon the geographic prevalence of the infection. With current HIV sero prevalence of 0.2 % among blood donors in India, NAAT with highest sensitivity and specificity would give minimal additional yield over and above the use of ELISA.
Sero prevalence of HBV isl.4% among blood donors based on programme data; and based on published data, it ranges from 2-5% in different parts of the country Sero prevalence of HCV is 0.4% among blood donors based on programme data and based on published data, it ranges from 1-2% in different parts of the country.
Additional yield using NAAT for HBV is 0.049% and for HCV is 0.016% as per Makroo study. The additional yield with NAAT for all three viruses combined (HIV, HBV and HCV) is 0.065% in Makroo study.
The unpublished data from the blood bank at KGMC, Lucknow shows an additional yield for HIV as 0.01% (4 additional yields out of 35722 tested), for HBV it is 0.30% (108 yields out of 35722 tested) and for HCV it is 0.13% (46 out 35722 tested) The data from blood bank at AIIMS (Data under publication in Transfusion Apheresis Sciences) shows: Additional yield for HIV is 1 in 73898 (0.0014%), for HCV is 37 in 73898 (0.05%), for HBV is 73 in 73898 (0.1%) As per these studies, it is evident that for HBV and HCV, the additional yield is low and is further low for HIV.
The study from Thailand Blood donation, the additional NAAT yields for HIV is 1: 97,000, for HBV 1: 2800 and HCV 1: 4, 90,000 also indicating low yield for HIV, HCV and HBV.
Add-on test The published data suggests that NAAT screening misses to detect viral markers. Therefore, it is clear that NAAT cannot be used as a stand-alone test to replace serological tests, which constitute the standard practice, and would clearly be an add-on test (in addition to the existing serological tests), which would also increase the cost of donor screening tremendously.
Positive Predictive Value Positive predictive value definition: Positive predictive value is a measure of the performance of a screening test to accurately diagnose the ntrue positives" The positive predictive vafue depends on sensitivity, specificity and disease prevalence in the population.
Furthermore, the positive predictive value of NAAT is expected to be low in countries with a relatively low population-based HIV prevalence, like India.
In view of this and the above issues related to sensitivity, NAAT tests cannot replace the antibody detection tests. At best it would be an add-on test to standard serological tests used to screen the donated blood.
Window Period The window period is the length of time following infection before the screening test becomes reactive (WHO, 2010). NAAT assays are shown to reduce the window period. HIV RNA can be detected by NAAT approximately 7 to 11 days after infection: i.e. when the results of HIV antibody assays are still negative, but HIV RNA is detectable (Kleinman et at, 1997; WHO, 2010). HIV antibody immunoassays have a minimum window period of 21 days.
HCV antibody becomes detectable approximately 30 to 60 days after infection. Viral antigen normally appears between 0 and 20 days after viral RNA first appears. Antibody is generated and can be detected between 10 and 40 days after antigen is first detected. HCV RNA is normally detectable within a few weeks of infection and persists for6-8 weeks prior to antibody sero conversion (Kleinman et al, 1997; WHO, 2010).
Window period for Transfusion Transmitted Infections (TTI) using various screening methodology is shown in the following Table.
TTI 3rd Generation ELISA 4th Generation ELISA Individual-NAAT HIV 21 DAYS 14 DAYS - 7 HCV 59 DAYS 10 DAYS - 7 HBV 39 DAYS 24 DAYS - 20 "Zero Risk" Not Achievable with Addition of NAAT Assays A "zero risk' cannot be achieved even if NAAT assays are added, since the window period would still remain as mentioned above (e.g., ~ 7 days for HIV). Despite the improvements in HIV testing, there have been reports of HIV-NAAT-negative blood involved in transfusion-transmitted HIV. Delwart et al reported transmission of HIV-1 from a NAAT negative donation with low viral load. (Vox Sang 2004;86:171-7). This demonstrates that despite the employment of the most sensitive type of assay to screen blood donations, zero risk is presently still unattainable.
WHO Recommendations WHO recommends that the introduction of NAAT should be considered only when an efficient and effective programme based on antibody/antigen testing is in place (Laperche et al, 2003) and there is a clear, evidenced, additional benefit. Although NAAT reduces the window period of infection, in countries with a low incidence of infection, the incremental gain is minimal as the number of donors in the window period at the point of donation is generally very low. However, in countries with a high incidence of infection, there are likely to be significant numbers of window period donations that can be identified by NAAT (Vermeulem et al, 2009). Thus although the risk of transfusing a blood unit collected during the window period may be decreased using NAAT, the actual benefit in most populations has first to be determined and should be balanced against the complexity and high cost of performing NAAT, including the infrastructure required (Postma et al, 2002; Straemer et al, 2004; van Hulst et al, 2008)..." (WHO, 2010).
HCV The multi-centric study from Indian blood banks (Makroo et al, 2008) did not find significant improvement in detection of HCV by NAAT. Of the 12,224 samples under study, NAAT yield was only 0.008%.
HBV The additional NAAT yield for HBV was 0.05% (n=6) in the same Makroo et al 2008 study. However, India is a country with only a moderate prevalence of hepatitis B, with the HBsAg carrier rate at 2.4% in the general (non-tribal) population (Batham et al, 2007).
Technical Expertise and Infrastructure NAAT assays are complex and highly demanding in terms of technical expertise and infrastructure. It requires stringent training and supervision, as well as an external quality assessment (EQA) programme (which is not available indigenously), since it involves target amplification (in both multiplex PCR, as well as Transcription Mediated Amplification (TMA)) and has a potential risk of generating false positive results.
Limited Number of Manufacturers of NAAT There is only a single manufacturer for an FDA-approved multiplex assay that simultaneously detects all 4 important blood borne viruses, HIV-1, HIV-2, HBV and HCV (Roche). If HIV-2 is excluded, there is one more manufacturer producing multiplex NAAT for HIV-1, HBV and HCV (S. No. 3 in Table 1; currently manufactured by Novartis). However, it should be noted that HIV- 2 infection was estimated at 1.3% of all HIV infections as per an indexed Indian publication, based on the screening of 1,75,026 blood donors (Kannagaiet al, 2010).
Additional Virus-Specific Testing Required following Multiplex NAAT The initial multiplex test does not identify individual viruses. For this, further testing has to be performed for each individual virus (on multiplex positive samples). This may lead to issues with expiry dates of individual kits; since positive samples are expected to be quite infrequent.
Closed Systems The equipment only supports reagents from the same manufacturer, i.e., the systems are closed not open (unlike equipment for immunoassays like EIA).
Turnaround Time The turnaround time for completing a NAAT assay is higher (6-8 hours) than that for EIA (2-3 hours).
5. The Committee has, thereafter, discussed about the Policy and the Regulatory Issues. They are as under:-
National Blood Policy The National Blood Policy was published by Government of India in the year 2002 with the objective to provide safe, adequate quantity of blood, blood components and products. The main aim of the policy is to procure blood from non-remunerated regular blood donors by the blood banks and eliminate profiteering by the blood banks by selling blood.
The Drugs and Cosmetics Act Human blood is covered under the definition of 'Drug' under Sec. 3(b) of Drugs a& Cosmetics Act, hence they are regulated under the Drugs & Cosmetics Act and rules there under.
The testing for HIV 1&2 antibodies of Whole Human Blood was made a mandatory requirement before transfusion following a notification issued in the year 1989 by Ministry of Health & Family Welfare (Govt of India).
As per Part XII B 'Requirements for the functioning and operation of a blood bank and/ or for preparation of blood components", Section K" Testing of Whole Blood"
"(2) Freedom from HIV antibodies (AIDS) Tests - Every licensee shall get samples of every blood unit tested before use, for freedom from HIV I and HIV II antibodies either from laboratories specified for the purpose by the Central Government or in his own laboratory. The results of such testing shall be recorded on the label of the container."
Disclosure of Results to Donors As per current policy, in case blood donors wish to know the results of their tests, they can choose this option. However, the kit insert of the Procleix Ultrio Assay (Novartis) states (on page 2 of its kit insert) that This assay is not intended for use as an aid in diagnosis of infection with HIV-1, HCV or HBV. The PROCLEIX ULTRIO PLUS Assay can be considered a supplemental test that confirms HIV-1 infection for specimens that are repeatedly reactive on a licensed donor screening test for antibodies to HIV-1." The potential false positivity of IMAAT could create downstream legal issues for the blood bank laboratory, due to contradictions by ICTC laboratory component of the programme, to which such individual donors are supposed to be referred and where HIV antibody testing with three rapid tests is still universally considered the gold standard for diagnosis of HIV infection.
OPERATIONAL ISSUES There would be operational challenges with mandating NAAT.in all licensed blood banks. It would necessitate significant amendment of the licensing conditions for operating blood banks, adding to the infrastructure, equipment's and manpower requirements. The blood transfusion services of the country would require to be considerably restructured, which may limit access to blood in remote and underserved regions.
NAAT Testing centres would require to be set up at state/ regional/ zonal locations with introduction of new testing algorithms and added logistics of sample transport. As per Makroo study, out of 12,794 samples received from well-developed centers round the country, 570 were not acceptable for testing.
There would be a delay in utilization of blood and components, especially platelets, which have a shelf life of only five days due to a higher turnaround time of NAAT testing.
ALTERNATIVE STRATEGIES For quality, safety and efficacy of blood and blood products, well-equipped blood centres with adequate infrastructure and trained manpower is an essential requirement. To attain maximum safety, the requirements of good manufacturing practices and implementation of hemo vigilance and quality systems moving towards total quality management are of paramount importance.
Efforts towards recruitment and retention of voluntary, non remunerated blood donors through education and awareness programmes, and phasing out of replacement blood donors in a time bound manner must be intensified.
Due emphasis on pre donation screening and post donation counseling of blood donors is necessary to achieve zero risk from transfusion as shown that centers which do pre donation screening and counseling have a much lower incidence of TTI in donors.
The above are existing provisions in the National Blood Policy 2002.
6. In it's final conclusions, the Committee has observed as under:-
NAAT can at best be an add-on test of screening for HIV along with routine mandated antibody screening tests by immunoassay NAAT assays may not provide zero risk for acquiring transfusion transmitted infections as it does not completely eliminate window period.
NAAT is technically demanding and our blood banks are presently not equipped enough to carry it out for service purpose.
NAAT may help to detect infinitesimally small proportion of additional positive samples at a great cost.
There is no proficiency testing available in India and one needs to depend on costly panels imported from abroad. Hence QA/QC will be a challenge.
There are many operational challenges inherent with introduction of mandatory NAAT testing, including limited numbers of manufacturers and closed systems.
There is merit in considering NAAT only after proper infra-structure and expertise is developed at the blood bank level.
Procuring blood from voluntary non remunerated repeat blood donors after proper donor screening and counseling, along with strengthening systems for hemo vigilance and quality management can help ensure a safe blood supply.
7. The final recommendations of the Committee are as under:-
The Committee examined as to what extent the PCR test could be made mandatory at all licensed blood banks across the country.
I The committee recommends that NAAT test should not be made mandatory for all licensed blood banks as NAAT does not completely eliminate window period, hence does not provide zero risk of transmission of TTI.
High turnaround time in screening the donated blood may lead to a delay in utilization and may compromise accessibility of blood and blood components.
Introduction would necessitate amendment in regulatory framework.
II The expert group further opined that in view of a paucity of India specific published data on additional yield of TTI viral markers as well as operational and technical feasibility; selected centres may be identified based on a scientific protocol and introduce NAAT test to generate the data to support future decision making.
8. Having gone through the entire report of the Committee, we are of the opinion that we should not issue any writ, order or direction on the respondent authorities to include Polymerase Chain Reaction (PCR) Test in the Standard H.I.V (Human Immuno Deficiency Virus) testing for blood transfusion in order to detect HIV infection. We are taking this view considering the settled proposition of law that in examining a question of the nature where a policy was evolved by the Government, judicial review thereof is limited. On matters affecting policy and requiring technical expertise, the Court should leave the matter to the experts who are qualified to redress the issues. Unless the policy or action is inconsistent with the Constitution and the laws are arbitrary or irrational or abuse of powers, the Court will not interfere with such matters.
9. In TATA Iron and Steel Co. Ltd. v. Union of India and another, reported in (1996) 9 SCC 709, the Supreme Court passed the following observations in paragraph 68 :
68. At this juncture, we think it fit. to make a few observations about our general approach to the entire case. This is a case of the type where legal issues are intertwined with those involving determination of policy and a plethora of technical issues; In such a situation, courts of law have to be very wary and must exercise their jurisdiction with circumspection for they must not transgress into the realm of policy making, unless the policy is inconsistent with the Constitution and the laws. In the present matter, in its impugned judgment, the High Court had directed the Central Government to set a Committee to analyse the entire gamut of issues thrown up by the present controversy. The Central Government had consequently constituted a Committee comprising high level functionaries drawn from various Governmental/institutional agencies who were equipped to deal with the entire range of technical and long-term considerations involved. This Committee, in reaching its decision, consulted a number of policy documents and approached the issue from a holistic perspective. We have sought to give our opinion on the legal issues that arise for our consideration. From the scheme of the Act it is clear that the Central Government is vested with discretion to determine the policy regarding the grant or renewal of leases. On matters affecting policy and those that require technical expertise, we have shown deference to, and followed the recommendations of, the Committee which is more qualified to address these issues.
10. In State of U.P. and others v. Ranusagar Power Co. and others, reported in (1988) 4 SCC 59, the Supreme Court passed the following observations in paragraph 76 :
76. Shri Trivedi, learned Additional Advocate-General, State of Uttar Pradesh drew our attention to the case of Panama Canal Company v. Grace Line, 356 U.S. 309 2 Lawyers' Edn. 788, where at page 793 of the report while dealing with the facts of that case Justice Douglas observed that, as it was seen in that case, the conflict raged over questions that at heart involved problems of statutory construction and cost accounting: whether an operating deficit in the auxiliary or supporting activities was a legitimate cost in maintaining and operating the Canal for purpose of the toll formula. These are matters on which experts might disagree; these involve nice issues of judgment and choice, which required the exercise of informed discretion. In those circumstances Justice Douglas observed that the case was, therefore, quite unlike the situation where a statute created a duty to act and an equity court was asked to compel the agency to take the prescribed action. What was emphasised was that the matter should be far less cloudy, much more clear for courts to intrude. It is also in this connection necessary that if technical considerations are involved the Court feels shy to interfere. Reliance was placed on the observations of this Court in Vincent Panikurlangara v. Union of India and others,  2 S.C.C. 165. There the writ petition involved the claim for withdrawal of 7000 fixed dose combinations and withdrawal of licences of manufacturers engaged in manufacture of about 30 drugs which have been licensed by the Drugs Control Authorities; the issues that fell for consideration are not only relating to technical and specialised matters relating to therapeutic value, justification and harmful side effects of drugs but also involved examination of the correctness of action taken by respondents 1 and 2 therein on the basis of advice; the matter also involved the interest of manufacturers and traders of drugs as also the interest of patients who require drugs for their treatment. This Court reiterated that in view of the magnitude, complexity and technical nature of the enquiry involved in the matter as also the far-reaching implications of the total ban of certain medicines for which the petitioner had prayed, a judicial proceeding of the nature initiated was not an appropriate one for determination of such matters. The technical aspects which arose for consideration in a matter of that type could not be effectively handled by a court. This Court also reiterated that similarly the question of policy which was involved in the matter was also one for the Union Government keeping the best interest of citizens in view to decide. No final say in regard to such aspects came under the purview of the court.
11. We direct the respondent authorities to bear in mind that in view of the dangers inherent in supply of contaminated blood, it must be ensured that the blood that is available with the Blood Banks for use is health and free from infection.
12. We do not propose to go any further in the matter after considering the report of the expert Committee. In light of the above, we close this Public Interest Litigation. In the facts and circumstances of the case, there shall be no order as to costs.
13. Since we are disposing of the main writ-petition, being PIL No. 156 of 2012, the connected CAs would also not survive and are being disposed of accordingly.
(BHASKAR BHATTACHARYA, C.J.) (J.B.PARDIWALA, J.) Mohandas Page 21 of 21