NAT Yield Research Articles

NAT yield in blood donors: An observational study.

Individual donation nucleic acid testing (ID-NAT) is considered as highly sensitive technology for viral transfusion-transmissible infections (TTIs) in blood donors. The present study was aimed to analyze the results of ID-NAT with special reference to different types of donors, their age, gender, blood group ranges in a tertiary care center in north India. The present study was done from 24th June 2019 to 31st December 2021 in Blood Center, Department of Immunohematology and Blood Transfusion, SMS Hospital, Jaipur. A total of 18313 apparently healthy adult donors were included in present study. In 2019 Combined NAT yield was 1 in 754, in 2020 it was 1 in 2368 and in 2021 it was 1 in 741. With Total NAT yield was 1 in 1017 (0.09 %) over a period of study. NAT yield in HBV is 1 in 1077, in HCV 1 in 18313 and no NAT Yield in HIV. NAT testing for hepatitis B provides additional safety because ELISA does not pick up occult hepatitis. The non-seroconverting or delayed seroconverting disease is missed by ELISA alone and can be picked up by NAT.

Hepatitis B, C And Hiv Exposure On Nat And Clia Blood Examination Methods At Regional Blood Centre Abbottabad.

Blood transfusion is a lifesaving method in clinical emergencies. Despite various preventive measures, the spread of Hepatitis B, C and HIV remains a big issue in Pakistan. This study was done to describe transfusion transmitted diseases using NAT and CLIA techniques, on exposure to these viruses. This study was conducted from 1st April to 25th August 2022. A descriptive study was done along with univariate analysis. The data was obtained from the regional blood centre in Abbottabad and it consists of reactive and non-reactive cases of NAT and CLIA in the sample size of 6233 donors. Data was collected from donors, and selected according to predefined criteria. In 6233 samples, 53 were reactive for either Hepatitis B, C or HIV. Forty-seven were reactive with both CLIA and NAT. 6 were reactive with NAT only and 6107 were non-reactive. NAT yield detected in this study is 0.096%. (1:1039 donations). It implies that NAT should be the preferred method for screening in blood banks.

High Yield of Minipool NAT in India using a Sensitive Multiplex Assay for Blood Donor Screening

Background and Objectives: Nucleic acid amplification testing (nucleic acid testing [NAT]) for blood donor screening is increasingly being adopted in India to reduce the risk of transfusion-transmitted diseases. The high sensitivity of NAT enables testing of a large volume of donations in minipool format; reducing the costs of testing compared to individual donation testing. This study was aimed at evaluating the yield of minipool NAT testing for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) in blood donors from Uttar Pradesh. Methods: Samples from routine blood donors collected between August 16, 2016, and December 31, 2020, that were seronegative for hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, syphilis, and malaria were further screened by NAT in pools of six donations (MP6) using the cobas TaqScreen MPX Test, version 2.0 (MPX2) on the cobas s 201 System. Members of reactive pools were tested to identify the reactive donation(s). Viral load testing was performed on randomly selected NAT-reactive samples. Results: Of 172,443 seronegative donors, 463 were NAT reactive: 369 HBV, 89 HCV, 2 HIV, and 3 co-infected with HBV and HCV. The overall NAT yield was 0.27%, with individual virus yield rates of 1/464 for HBV, 1/1874 for HCV, and 1/86,222 for HIV. Viral load testing of 19 HBV NAT-yield donations showed low concentrations in 16 samples and undetectable viral load in three; the two HCV NAT-yield donations tested had high viral loads. Conclusion: Screening of blood donations by minipool NAT using the highly sensitive MPX2 assay identified a high yield of serology negative, NAT-positive donations, including HBV reactive donations with low viral concentrations.

HIV incidence in South African blood donors from 2012 to 2016: a comparison of estimation methods.

Measuring incidence is important for monitoring and maintaining the safety of the blood supply. Blood collected from repeat-donors has provided the opportunity to follow blood donors over time and has been used to estimate the incidence of viral infections. These incidence estimates have been extrapolated to first-time donors using the ratio of NAT yield cases in first-time versus repeat-donors. We describe a model to estimate incidence in first-time donors using the limiting antigen (LAg) avidity assay and compare its results with those from established models. HIV-positive first-time donations were tested for recency using the LAg assay. Three models were compared; incidence estimated for (1) first-time donors using LAg avidity, (2) first-time and repeat-donors separately using the NAT yield window period (WP) model and (3) repeat-donors using the incidence/WP model. HIV incidence in first-time donors was estimated at 3·32 (CI 3·11, 3·55) and 3·81 (CI 3·07, 4·73) per 1000 PY using the LAg assay and NAT yield WP models, respectively. Incidence in repeat-donors was between 2·0- and 2·5-fold lower than in first-time donors estimated at 1·56 (CI 1·37, 1·77) and 1·94 (CI 1·86-2·01) per 1000 PY using the NAT yield/WP and incidence/WP models, respectively. Testing HIV-positive donations using the LAg assay provides a reliable method to estimate incidence in first-time donors for countries that collect the majority of blood from first-time donors and do not screen with NAT.

Improved detection of early acute, late acute, and occult Hepatitis B infections by an increased sensitivity HBsAg assay

BackgroundHepatitis B surface antigen (HBsAg) is the primary marker for diagnosis of acute and chronic hepatitis B. Although HBsAg assays have undergone continuous improvement, gaps remain in the detection of early and late acute infection and occult hepatitis B infection (OBI). ObjectivesThe performance of a prototype, improved sensitivity HBsAg assay run on the ARCHITECT and Alinity instruments was evaluated for detection of early and late acute infection and OBI. Study designSeventy seven early acute samples [positive only for hepatitis B viral DNA (HBV DNA)], twelve seroconversion panels spanning late acute infection, and 101 occult samples (HBsAg negative, positive for HBV DNA and anti-HBc) were tested with the prototype assay and ARCHITECT HBsAg Qualitative II. HBsAg gene sequencing was performed to determine genotype and mutations in the immunodominant region. ResultsCompared with ARCHITECT HBsAg Qualitative II, the prototype assay showed increased detection of NAT yield samples (28/77, 36.4%,), late acute samples (≥13 days longer detection of HBsAg for 6/12 panels), and OBI samples (11/101, 10.9%). HBsAg sequence data were obtained for 62 samples. Genotypes represented were A1, A2, B2, B4, C1, C2, C5, D3, E, and H. HBsAg escape mutations were found in 4.8% of NAT yield and 38.9% of OBI samples sequenced. Prototype assay values for 188 samples were equivalent on the ARCHITECT and Alinity instruments. ConclusionsThe new prototype HBsAg assay will be of diagnostic value in providing improved detection of early acute, late acute, and occult HBV infections.

Effectiveness of blood donor screening by HIV, HCV, HBV-NAT assays, as well as HBsAg and anti-HBc immunoassays in Germany (2008-2015).

Background and ObjectivesIn Germany, in addition to standard blood donor screening, further mandatory tests were introduced for HCV‐RNA, HIV‐1‐RNA and for anti‐HBc. Screening for HBV‐DNA is optional. This study investigates the benefits of these additional tests for the detection of HIV, HCV, and HBV infections among German blood donors.Materials and MethodsFrom 2008 to 2015 we collected data on blood donations exclusively testing NAT positive (NAT yield) or reactive in only one of the screening assays. Assuming a Poisson distribution, we calculated NAT yield/reactive only rates on a per donation basis (number of yield/reactive only cases divided by the number of donations tested in the period under review) with 95% confidence intervals.ResultsResponding establishments covered 95% of the donations. We identified 20 HIV‐1‐NAT, 61 HCV‐NAT and 29 HBV‐NAT yield cases among approximately 46 million blood donations tested corresponding to 0·43 HIV‐1 NAT, 1·32 HCV‐NAT, and 0·64 HBV‐NAT yield cases per million blood donations tested. For one HBsAg reactive only case and 23 anti‐HBc reactive only cases in repeat donors, infection was confirmed by ID‐NAT which translates into 0·02 and 0·55 cases per million donations tested. During the 8‐year‐observation period, one HIV‐1, no HCV and four HBV transmissions associated with donations in the viremic pre‐seroconversion window period were reported.ConclusionAnnually, NAT screening alone detected 2·5 HIV‐1, 7·6 HCV, and 3·6 HBV infectious donations; anti‐HBc screening alone identified 2·9 infectious donations of repeat donors with occult HBV infection. Overall, the survey results support that the currently practiced donor HIV/HCV/HBV screening strategy in Germany does ensure a high standard of blood safety.

Initial trends of individual donation nucleic acid testing in voluntary & replacement donors from a tertiary care centre in north India.

Background & objectives:Individual donation nucleic acid testing (ID-NAT) is considered as sensitive technology to assess blood safety from viral transfusion-transmissible infections (TTIs) in blood donors. The present study was aimed to analyze the results of ID-NAT for three years (2013-2015) with special reference to different types of donors and their age ranges in a tertiary care centre in north India.Methods:The results of ID-NAT for three years were retrospectively analyzed at our centre. A total of 168,433 donations were tested with ID-NAT, of which 10,467 were tested with Procleix® Ultrio® reagents and 157,966 were tested with Procleix® UltrioPlus® reagents, and the results were compared with those of serology to calculate the NAT yield in voluntary, replacement, first-time and repeat donors.Results:A combined NAT yield was observed as one in 1031 out of 167,069 seronegative donations with HBV yield as one in 1465, HCV yield as one in 3885 and HIV-1 as one in 167,069. Yield for co-infection (HCV and HBV) was one in 41,767. A high NAT yield was observed in replacement donors (1 in 498) as compared to voluntary donors (1 in 1320).Interpretation & conclusions:Addition of NAT to serology improved the blood safety in our centre interdicting possibility of 150 TTIs annually. It has also reemphasized the safety of voluntary over replacement donors. The results also highlight the need of proper counselling, notification and referral guidelines of NAT yield donors in our country and other countries which lack them.

A nucleic acid amplification repeat testing algorithm reveals high risk of hepatitis B and C transmission with serologic blood screening practice in Punjab, India

BackgroundLack of confirmatory testing of reactive donations for hepatitis C (HCV), B (HBV) and human immunodeficiency (HIV) viruses hampers reliable residual transmission risk analysis in India.Materials and MethodsIn our centre, 39 295 blood donations were tested for HIV Ag/Ab, anti‐HCV and hepatitis B surface antigen (HBsAg) by a variety of ELISAs and in parallel by individual donation nucleic acid amplification technology (ID‐NAT). NAT yields were confirmed by triplicate repeat reactivity in primary test‐tube and fresh frozen plasma (FFP) samples as well as by viral load (VL) testing and supplemental serologic assays.ResultsNAT and serology concordant reactive results included 23 (0·06%), 290 (0·74%) and 254 (0·65%) donations for HIV, HCV and HBV, respectively. Additionally, 15 HCV (1/2620) and 29 HBV (1/1355) seronegative NAT yield donations were confirmed. HBV marker testing identified three (1/13 100) window period (WP), 25 (1/1637) occult HBV infection (OBI) and one anti‐HBs breakthrough infection. ID‐NAT has reduced residual risk of infection from 1/2600 to 1/270 000 for HCV WP, 1/8000 to 1/21 000 for HBV WP and 1/11 000 to 1/66 000 for OBI.ConclusionA NAT repeat test algorithm was instrumental for confirmation of viral infection and revealed high residual risk of hepatitis B and C transmission by the practiced ELISA blood testing.

Blood safety implications of donors using HIV pre-exposure prophylaxis.

HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection. The most commonly used PrEP medication (Truvada® , Gilead Sciences, Inc.) acts by inhibiting HIV-1 reverse transcriptase. If someone who is using PrEP unknowingly becomes HIV infected (termed 'PrEP breakthrough infection'), there may be suppressed viral replication resulting in a virus level undetectable by the most sensitive HIV NAT. Failure to seroconvert and seroreversion (loss of previously detectable HIV antibodies) have also both been observed with 2nd, 3rd and 4th generation screening immunoassays, as well as Western blot assays. If such a person was tested in the course of donating blood, the results may therefore be difficult to interpret. The index of suspicion for possible PrEP 'interference' should be highest in the context of concomitant low-level positive or 'greyzone' reactivity on HIV NAT and serological tests, which is an unusual pattern in acutely HIV-infected blood donors. Another possibility is detectable HIV RNA with negative HIV serology (i.e. a potential 'NAT yield' case) but without subsequent HIV seroconversion (or disappearance of HIV RNA). Excluding antiretroviral therapy or PrEP use by the donor in such circumstances would be important. The current rarity of PrEP breakthrough infection indicates that any potential safety risk is likely very small. However, considering the increasing use of PrEP we feel it is prudent for those interpreting HIV donor screening test results to consider the potential for PrEP interference.

Comparison of two algorithms to confirm and discriminate samples initially reactive for nucleic acid amplification tests.

BACKGROUND:Blood centers in India have published individual donor nucleic acid testing (ID-NAT) data based on an algorithm (Algorithm A) where serologically negative, NAT reactive sample was subsequently tested with discriminatory NAT (d-NAT), and on the basis of d-NAT, initial reactive samples were classified as “NAT yield” or inconclusive. We followed Algorithm B based on replicate testing and Ultrio Plus assay and compared the results with Algorithm A with Ultrio assay.MATERIALS AND METHODS:Results of ID-NAT using two algorithms were analyzed.RESULTS:A total of 88,583 (31,844 with Algorithm A and 56,739 with Algorithm B) samples were tested. Among serology nonreactive donations, NAT inconclusive results came down from 95.2% in Algorithm A to 73.1% in Algorithm B (P = 0.0001). Discriminated yield (DY) rate went up from 4.7% in Algorithm A to 21.9% in Algorithm B (P = 0.001).CONCLUSION:The study data suggest that replicate testing strategy and Ultrio Plus reduce the number of “inconclusive results” seen with earlier commonly used algorithm. We recommend a replicate testing strategy in ID-NAT testing since it will increase the DY and will eliminate the unnecessary discriminatory tests.

Three-Year Experience in NAT Screening of Blood Donors for Transfusion Transmitted Viruses in Croatia

Background: Croatia implemented individual donation (ID)-NAT testing of blood donors in 2013 for three viruses HBV, HCV, and HIV-1 as a mandatory test for all blood donors. This study assessed the impact of NAT screening 3 years after its implementation. Methods: A total of 545,463 donations were collected and screened for HBV, HCV, and HIV-1 using the Procleix Ultrio Plus Assay. All initially reactive (IR) NAT samples were retested in triplicate and, if repeatedly reactive (RR), NAT discriminatory assay (dNAT) was performed. ID-NAT positive donations were confirmed by RT-PCR on the COBAS AmpliPrep/TaqMan platform. Results: Out of 545,463 samples tested, 108 (0.02%) were RR in NAT. There were 82 (75,9%) HBV reactive, 16 (14.8%) HCV reactive, and 10 (9.3%) HIV-1 reactive samples. 51 (47.2%) samples were ID-NAT positive only. Out of these 51 NAT yield cases, 1 window period HIV-1 and 50 occult HBV infections (OBI) were determined. There were only two potential HBV DNA transmissions from OBI donors. Conclusion: The implementation of NAT screening for three viruses has improved blood safety in Croatia. During the 3-year period, 1 window period HIV-1 and a number of occult HBV donations were identified.

NAT positivity in seronegative voluntary blood donors from western India

Background and objectivesPrevalence and composition of Hepatitis B, Hepatitis C and HIV-1, NAT positive but seronegative voluntary blood donors from western part of India is yet to be documented. Material and methodsOver last 2 1/2 years all the seronegative voluntary blood donors were tested using 10 minipools on a semiautomated NAT testing platform. The positively tested donors were followed up for at least five months for development of seropositivity. Results79532 seronegative donations were tested by 10 minipool (MP) NAT leading to 51 positive sample (44 Hep B, 5 HIV 1 and Hep C positive). All the HIV and Hep C NAT positive donors eventually developed seropositivity and out of 44 Hep B NAT positive donors, 31 developed seropositivity within six months of follow up, following counseling of the donors. This data translate into NAT yield of 1:1559 donors for all virus taken together. NAT yield for Hep B 1:1807 donors were much higher than HIV 1 in 1:15906 and HCV yield of 1:39761. Semiautomated minipool NAT testing system was found to be cost effective way for improving blood safety. Interpretation and conclusionSeronegative NAT yield in voluntary blood donors are quiet high in western part of India and in line with rest of the country is mainly due to Hepatitis B infection. Implementation of strict donor screening, Hep B vaccination of the population and sample mutation of NAT testing should be under taken on war footing.

Detection of different categories of hepatitis B virus (HBV) infection in a multi‐regional study comparing the clinical sensitivity of hepatitis B surface antigen and HBV‐DNA testing

Twenty-two users of individual donation nucleic acid amplification technology (ID-NAT) in six geographical regions provided detailed hepatitis B virus (HBV) infection data in first-time, lapsed, and repeat donations and classified confirmed HBV-positive donors into different infection categories. These data were used to compare the clinical sensitivity of hepatitis B surface antigen (HBsAg) and HBV-DNA testing. In total 10,981,776 donations from South Africa, Egypt, the Mediterranean, North and Central Europe, South East Asia, and Oceania were screened for HBV-DNA using the Ultrio assay (Grifols/Hologic) and for HBsAg using a chemiluminescence immunoassay, and 9455 HBV-infected donations were identified. HBsAg-negative window period (WP), HBsAg-positive and occult HBV infection (OBI) stages were determined using supplemental serology, quantitative polymerase chain reaction, and replicate multiplex and discriminatory HBV NAT test strategies. For two regions, additional data sets using the more sensitive Ultrio Plus assay were assessed. Regional HBV detection rates in first-time donors varied between 0.08% and 1.07%, with WP NAT yield rates varying between 1:7700 and 1:294,000 and OBI NAT yield rates varying from 1:3900 to 1:59,000. HBsAg CLIA detected 97.0% of infections in first-time donors, 62.7% in lapsed donors, and 41.0% in repeat donors; whereas Ultrio detected 93.1%, 95.0%, and 98.3% of infections in these respective groups. HBV-DNA detection rates in HBsAg-positive donors varied from 90.2% to 96.3% between regions but increased significantly (range, 95.2-98.2%) with the Ultrio Plus assay. ID-NAT and serology are complementary in detecting HBV infection in first-time donors, but HBV-DNA is superior to HBsAg detection in repeat donors.

Significance of nucleic acid testing in window period donations: Revisiting transfusion safety in high prevalence-low resource settings

Background: Safe blood transfusion to the people is essential requirement of health care delivery system. Despite the mandatory screening of blood with newest, very sensitive serological test, considerable risk remains for transfusion transmission of virus due to window period infections. Study was aimed to analyze the efficacy of Mini pool Nucleic Acid Amplification Testing as additional donor screening program and its role in improving blood safety in the high prevalence population. Material and Methods: Study was performed at a tertiary-care, accreditated hospital from June 2013 to December 2015 All negative cases for anti-HIV, anti-HCV and HBsAg by ELISA were subjected to MP-NAT to detect HIV-1, HIV-2 and HCV-RNA with HBV DNA.Results: In 31 months, 20470 donations were received of which whole blood donations were 16997 (83.03%) and 3473 (16.97%) apheresis. Out of 16997 donations, 446 (2.61%) were seroreactive. Out of 16551 sero-negative donors subjected to MP-NAT testing, 17 (0.10%) were NAT reactive (NAT yield -1 in 974). Out of 17 cases, 12 were HBV (1 in 1379), four HCV (1 in 4138) and one HIV NAT reactive (1 in 16551). Conclusion: NAT has improvised the blood safety by detecting the virus in the pre-seroconversion, window period thereby providing much higher sensitivity as compared to newest generation serological tests. In countries with high incidence of infection with significant number of window period donations, NAT can serve as a valuable tool along with other serological testing in high prevalence, resource constrained countries to achieve the goal of zero risk of blood.

Five years of experience with ID‐NAT at a tertiary care centre in North India: An interdictory step in preventing the transfusion‐transmitted Infections

IntroductionTechnological advancements in transfusion medicine have led to safer blood supply to the community like never before. However, blood safety is a daunting task in India with ~1.25 billion population and high prevalence rate of HIV (0.29%), HBV (2–8%) and HCV (2%) in donor population. This study aims at evaluating the impact of ID‐NAT as an add‐on test on safe blood supply in the current Indian scenario.Materials and MethodA retrospective observational study was conducted to analyse the data of 5 years of add‐on NAT at Main Blood Bank, AIIMS, New Delhi.Results1.84% (3556 of 193 167) units were initially NAT reactive. A total of 3495 units were further tested, of which 79.25% were discriminated (193 HIV, 421 HCV, 2060 HBV and 96 co‐infections). The remaining 13% (456) were repeat non‐reactive and 7.7% (269) could not be discriminated. Overall, NAT yield rate was one in 847, whereas virus‐specific NAT yield rates were one in 96 584, one in 2683, one in 1370 and one in 14 859 for HIV, HCV, HBV and HBV/HCV Co‐infections, respectively.ConclusionFive‐years of ID‐NAT screening interdicted 228 probable TTIs to 684 (assuming 100% component separation) transfusion recipients. Implementation of NAT along with routine serological tests for screening of the blood donations definitely improves the transfusion safety. However, interpretation of NAT reactive results should be adjudged cautiously keeping in mind, the chance occurrence of false‐positive reactivity.

Two years' experience of implementing molecular screening of hepatitis B virus, hepatitis C virus and human immunodeficiency virus 1, 2 in Riyadh blood donors

Molecular screening technologies have improved blood safety by reducing the number of window-period transmissions relative to serological screening. In the two years following the introduction of molecular testing in King Khalid University Hospital, Saudi Arabia, 25,920 donor samples were screened in parallel by both serological and molecular techniques for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). No HCV or HIV NAT yields were detected. However, molecular screening enabled the interdiction of two confirmed HBV NAT yields. This is only the second report of confirmed HBV NAT yield in the Kingdom of Saudi Arabia, and amongst the few reports in the wider Middle East and North Africa region.

Confirmation and follow up of initial “NAT yields”: Prospective study from a tertiary healthcare center in India

BackgroundIn India variable rate of “NAT yield” has been demonstrated in several published reports. This study was performed with the objective to know the rate of “true NAT yield” in blood donors by confirmation with supplementary tests and follow up of initial “NAT yield” donors. Materials and MethodsA total of 48,441 blood donors were tested for HIV, HBV and HCV with enhanced chemiluminescence and ID-NAT. To know the true NAT yield status confirmation of NAT yield donors was done as with an array of serological tests, repeat ID-NAT and alternate NAT. ResultsThe cumulative initial “NAT yield” rate was 1:4404 (11/48,441). Seven of 11 initial “NAT yields” were for hepatitis B whereas two each were in HIV and HCV. Among the 11 “NAT-yield” donors, eight donors were followed-up for confirmation. Out of these eight donors only 4 were found to be true HBV NAT yields. Out of four true NAT yields two were window period donations while the other two were occult hepatitis B infection with anti-HBcore total positive. ConclusionOur findings suggest that all “initial NAT yields” may not be “true NAT yields”. We would also like to suggest that to demonstrate the true “NAT yield” status supplementary tests and donor follow up are important to differentiate true NAT yields.

Serological characterization of occult hepatitis B virus infection among blood donors in India.

Discovery of hepatitis B infections characterized by the presence of viral genome without detectable HBsAg (Occult Hepatitis; OBI) has initiated a considerable amount of research in this regard. Our study is a serological and molecular characterization of OBI among the donors who donated at our blood bank during the study period. During the study period HBsAg ELISA non reactive ID-NAT reactive donors samples were screened for presence of antibody against HBc, HBs and HBe. Molecular analysis of these NAT yield samples was undertaken for detection of the viral load and genotyping. We studied 28,134 HBsAg ELISA non reactive donor samples. On testing them with ID-NAT, HBV DNA was detected in 25 samples. Eighteen samples out of these 25 NAT yield were further worked up. The 66.6% of the NAT yield samples (12 out of 18) were reactive for antibody against HBc. The 25% (3 out of 12) of these NAT yield samples having antibody against core antigen also had antibody against HBs. The 27.7% (5 out of 18) of NAT yield detected by ID-NAT did not have any detectable serological marker in blood. Four out of 12 core antibody positive NAT yield samples had genotype A HBV infection. As per our study molecular detection of HBV DNA by ID-NAT, we were able to analyze 18 HBV NAT yield cases among 28,134 HBsAg ELISA non reactive donors. Out of 18, 12 donors were OBI whereas the rest (6) were in window period (WP yield) of HBV infection. One out of every 3.6 NAT yield detected by ID-NAT was non reactive for all serological markers.

Enhanced detection of hepatitis B virus in Hong Kong blood donors after introduction of a more sensitive transcription‐mediated amplification assay

A total of 517,072 and 399,326 consecutive donations were screened for hepatitis B virus (HBV) by individual-donation nucleic acid testing (ID-NAT) using Ultrio and Ultrio Plus assays (Novartis Diagnostics), respectively. The impact of more sensitive HBV detection by the latter assay version was established by comparing NAT yield and transmission risk. Donations were screened simultaneously for HBV serologic markers and ID-NAT, followed by discriminatory assay and confirmatory test algorithms. Window period (WP) reduction and residual HBV transmission risk were computed using mathematical modeling. HBV NAT-yield rates for both WP and occult HBV infection (OBI) increased significantly from 1:34,471 to 1:17,362 (p = 0.036) and from 1:5120 to 1:2450 (p < 0.0001), despite a 1.2- and 1.6-fold decrease in hepatitis B surface antigen (HBsAg) incidence and prevalence rates respectively. After adjusting for this bias, the WP and OBI NAT-yield improvement factors were 2.3 and 3.4, respectively, higher than a less than 1.5-fold increase estimated from analytical sensitivity studies on HBV Genotype A and C standards. The current WP transmission risk with Ultrio Plus screening was estimated at 1:55,000 compared to 1:22,000 with HBsAg testing. The observed greater than twofold enhanced WP NAT yield with the Ultrio Plus assay can be explained by greater than 10-fold increased analytical sensitivity in detecting the HBV Genotype B and C strains in Hong Kong. Direct comparison studies of the two assay versions on dilutions of HBV NAT-yield samples are required to confirm this hypothesis.

Current concepts in transfusion transmitted diseases

During the 1950s, 25% of recipients of four or more whole blood transfusions in New York City, USA, developed jaundice, and this was accepted as a ‘fact of life’. At that time, the only transfusion transmitted infectious diseases (TTID) of importance were syphilis and ‘serum hepatitis’, later recognized as hepatitis B. Syphilis screening was introduced in the 1940s and the first assays for hepatitis B surface antigen in the early 1970s. In the early 1980s, the tragedy of AIDS brought serious consequences for blood recipients but also brought attention and resources to the prevention of TTID, resulting in the introduction of additional screening tests in the U.S. and in several other countries [1]. As new screening tests, donor screening procedures and quality systems were developed, they were cumulatively added to the list of donor eligibility and blood processing requirements. Obsolete procedures were removed only under exceptional circumstances. Gradually, multiple layers of safety became part of regulatory requirements including in addition to testing and quality systems, more extensive donor history questionnaires in which donors are asked about potential exposure to transmissible agents (e.g. history of risk behaviours, travel); deferral files listing donors who were deferred because of travel, risk behaviour or reactive screening tests results; quarantine of untested and unsuitable components, kept separately to avoid inappropriate release for transfusion. It should be noted that donor history questions [2] and deferral files [3] have lower sensitivity and poorer predictive value than donor screening tests. In addition, requirements for donor notification and counselling after positive test results were instituted under the presumption that knowledge about their positive results would discourage positive donors from returning to donate. Also, the movement towards volunteer, non-remunerated donations as opposed to replacement donations (made by donors referred by a patient to ensure admission to a hospital) or paid donations was intensified.