Our tryst with Nucleic Acid Testing Dolly Daniel, Dept of Transfusion Medicine, CMC, Vellore

CMC, Vellore A Large mission hospital > 100 years old Over 2200 IP beds Over 6000 OP a day About units of blood / components- annual usage Strong component of education / service and research

BB- Id Testing Only Hepatitis B testing 1988 – HIV 1997 – HCV All testing initiated before testing became mandatory for licensing

Why NAT at CMC??? Donor spread Seropositivity Anecdotal incidents of seroconversion

The American Red Cross accepts blood donations only from volunteer donors. Among Red Cross donors in a given year, 19 percent donate occasionally, 31 percent are first-time donors, and 50 percent are regular, loyal donors.

Detection of HIV-1 and HCV Infections among Antibody-Negative Blood Donors by Nucleic Acid– Amplification Testing -NEJM ,164,054 units screened Negative on serology 12 positive for HIV-1 RNA (1 in 3.1 million) (2 of which were detected by HIV-1 p24 antigen) 170 positive for HCV RNA ( 1 in 230,000) The respective rates of positive HCV and HIV-1 nucleic acid– amplification tests were 3.3 and 4.1 times as high among first-time donors as among donors who gave blood repeatedly Follow-up studies of 67 HCV RNA–positive donors demonstrated that seroconversion occurred a median of 35 days after the index donation Three cases of long-term immunologically silent HCV infection were documented

Donor Profile Almost 70% are replacement donors In the West – 100% Voluntary Repeat donors? ?? Process of deferral / self deferral / temporary / permanent and attitudes - very different

Linear Trend line

Issues Patient Safety (Staff requesting better ID screens) Quality of blood products One product being issued to even 5 babies

. Eskimo: "If I did not know about God and sin, would I go to hell?" Priest: "No, not if you did not know." Eskimo: "Then why did you tell me?"Eskimo: "Then why did you tell me?"” Annie Dillard

The Indian Experience – IJMR Feb 2008

India and NAT Total no of samples: Replacement donors : 8999 Voluntary donors : 3225 Seropositivity % – HIV, 0.33% HCV, 1.12% HBV

Seronegative but NAT positive Yield - 8 / Overall positivity – 1/1528 donations HIV - 1/ HCV / HIV 1 co infection- 1/12224 HBV – 6/12224

NAT testing would prevent 3272 infectious transfusions 818 HIV infected units 409 HCV infected units & 2454 HBV infected units from being transfused. If components are being processed – then double or triple these numbers

Translation to the CMC scenario Our donor distribution is very similar We have about donors bled each year X 2 / 3 components Approx 1/1500 transfusions infected Therefore about 35 of our patients are being infected annually by TTIs. (calculation of 2 components per donation)

CMC Stats IJMR seropos CMC seropos IJMR (NAT yield ) CMC Projected HIV 32 (0.26%) 70 (0.17%) 2 NAT pos /32 seropos 12 (4x3) HBV 137 (1.12%) 488 ( 2.19%) 6 NAT pos /137 seropos 54 (18x3) HCV 40 (0.33%) 214 (0.96%) 1 NAT pos /40 seropos 15 (5x3)

Institution 3 years …….. Justified Negotiated Presentations to clinicians

The process Challenges Infrastructure and space requirements Cost impact

Assessments Projected numbers of possible yields Health technology assessment Permitted on a trial basis

"The trouble with jogging is that by the time you realize you're not in shape for it, it's too far to walk back." Franklin Jones

The interim we waited….. No substitute for repeat voluntary donors No substitute for the practice of appropriate and rational use of blood

The Numbers Total Donors Screened – Sero positives – 594 Sero Negative

Seropositives HIV – 51 ( 0.18%) HBV – 364 ( 1.30%) HCV –179 ( 0.67%) Seropositive NAT Negative HIV – 37 HCV – 166 HBV - 49

Total seronegative units NAT positive – 68 Positive on repeat testing and discriminatory assays - 28 (0.105%) 1 per 950 donors approx)

Spread of positives HBV 22 HCV 3 HBV & HCV 2 HIV 1

One time positives and their significance ? ? False positives ? Low viral loads – Poissonian distribution Follow up recommended ?

Is it worth continuing? Cost per prevented infection At the cost of what?

He who sleeps on the floor will not fall off the bed. Robert Gronock..

In the context of transfusion services Has to be driven in the context of each individual institution Accessibility missing …… NAT available Basics of safe donor recruitment and appropriate use of blood and components

To conclude NAT seems to have worked for us… The confirmation of NAT yields is worth following up Working up samples which are one time NAT reactive – a must

Above all Each institution needs to thrash out the issue for itself Imperative that simple and safety measures like repeat voluntary donor recruitment and rational use of blood be focused upon alongside