Nucleic Acid Technology (NAT) testing for blood screening: impact of individual donation and Mini Pool – NAT testing on analytical sensitivity, screening sensitivity and clinical sensitivity

Abstract

Globally, in a number of countries the donated blood is screened for serology markers for the Human immunodeficiency diseases-1/2, the Hepatitis C virus (HCV), and the Hepatitis B virus (HBV). Several medium human development index (HDI) countries with reasonably high percentage of transfusion transmitted infections (TTI) are evaluating nucleic acid technology (NAT) assays to detect these viruses. Serology assays are performed on individual samples, while NAT is performed on either the individual donation (ID) or on a wide array of minipool (MP)-NAT testing formats. The limit of detection of ID-NAT assays equals the analytical sensitivity and that of pool testing reflects the pool size dependent decreased sensitivity also known as screening sensitivity. To many end users, it is not obvious that pool testing will have less sensitivity. In this review, mathematically predicted pool size dependent increase in risk days which is applicable to assays of all technologies is substantiated with published experimental results with NAT standards, clinical NAT only detected yields and detection misses by MP-NAT. In the second half, the blood banking system in India, the donor base, and the variables in serology testing are discussed to explain the wide range of reported NAT yields at 1/300 to 1/17 753. Currently, NAT is not mandated in India, and the cost-benefit value of NAT is being seriously debated. As <5 IU/ml of HIV-1 and HBV have resulted in TTIs, and nearly 83% of the HBV NAT yields in India have <20 IU/ml viral load, the most sensitive assay in the most sensitive format needs to be practiced to ensure maximum blood safety.

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

“…frequently not confirmed by repeat testing, or by testing for alternative markers [7,22,23]. The sensitivity of some of the ELISAs used in India is also suboptimal as is illustrated in our study where 10 out of 15 HCV WP NAT yields turned out to have detectable antibody by CLIA and seven of them also on retesting by a second more sensitive ELISA (data not shown).…”

“…The Punjab Province in India is near the border of Pakistan where two recent minipool NAT blood screening studies reported similar (or even higher) HBV and HCV yield rates than in our study, although NAT confirmation testing procedures differed. The serologic reactivity (in mainly first‐time donors) in India and Pakistan is frequently not confirmed by repeat testing, or by testing for alternative markers . The sensitivity of some of the ELISAs used in India is also suboptimal as is illustrated in our study where 10 out of 15 HCV WP NAT yields turned out to have detectable antibody by CLIA and seven of them also on retesting by a second more sensitive ELISA (data not shown).…”

“…: samples17,[19][20][22][23][24][25] and two were HBV-NAT yields;Table S2: samples 18, 27). (3) Three HCV and HBV dual infections were NAT yields for both targets(Table S1.…”

The validation and implementation of donor screening for hepatitis B virus, hepatitis C virus, human immunodeficiency virus 1/2 and syphilis by ultrio elite assay (Panther system) and chemiluminescence assay (Abbott Architect i2000SR system) in Namibia

“…Considering the hyper‐endemicity of HIV and HBV in Namibia at the time which was 16·8% for HIV and >8% for HBV , NAMBTS decided to keep TTI testing at SANBS to benefit from the ID‐NAT screening. Like many small economies, adding NAT to blood screening was not affordable for Namibia, but necessary for established blood safety measures and had to be adopted at all cost . Relocating blood screening with ID‐NAT to Namibia at that time was not cost‐effective for a small blood service such as Namibia which was collecting a volume of 18 000 blood donations annually.…”

Corrigendum

“…In , there is an error in Table 3 on page 320. The HIV‐1 value (7th column) for the bottom row should read ‘1600’ instead of ‘11600’.…”