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 75000 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 2004

37,164,054 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

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?"”   Annie Dillard

The Indian Experience – IJMR Feb 2008

India and NAT

• Total no of samples: 12224

• Replacement donors : 8999

• Voluntary donors : 3225

• Seropositivity - 0.26% – HIV,

0.33% HCV, 1.12% HBV

Seronegative but NAT positive

• Yield - 8 / 12224

• Overall positivity – 1/1528 donations

• HIV - 1/ 12224

• 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 27000 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 -2007-2008

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 – 26500

• Sero positives – 594

• Sero Negative - 25906

Seropositives

• HIV – 51 ( 0.18%)• HBV – 364 ( 1.30%)• HCV –179 ( 0.67%)

• Seropositive NAT Negative - 252• 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