Su Brailsford Consultant in Epidemiology and Health Protection NHS Blood and Transplant Colindale

Transfusion- The 3 R s Nottingham January 2015

Overview

What can be transmitted by transfusion ?How do we reduce the risk?

viralbacterial

How do we investigate a TTI?Are our risk reductions methods working?What does the future hold?

What can be transmitted by transfusion?

Viral infectionswindow period infectionthings we don t test forpreviously unknown infections

Parasitestravel?

Bacteriascreening of platelets-residual risk

Prionsno current screening test

Strategies to reduce risk of transfusion transmitted infections

DONOR SELECTION

PROCESSING, QUALITY CONTROL

SCREENING TESTS

STORAGE, PATHOGEN INACTIVATION

BETTER BLOOD

TRANSFUSION

TRACING

SURVEILLANCE

Modified from Bihl et al, Journal of Translational Medicine 2007, 5:25

Donor selectionBlood from volunteers is saferDonor selection process

Known infections: BBVs

Behavioural risks

Recent risks: Piercing

Travel history: malaria, WNV, T. cruzi

MaintainingSupply & cost

Minimisingrisk

We can t always test: vCJDMajor impact on blood safety measures in UK

Donor deferralTransfused donors

Active surveillance

Other measures

UK plasma no longer used for fractionationImportation of FFP for certain groupsReduce donor exposuresLeucodepletion

Current Testing StrategiesTimeline of introduction of microbiological tests for blood

donations, UK

And additional tests e.g. West Nile Virus

Infectious markers in donors

Infection rate in donors declining but

Viral TTIs still happen, investigated when:Post-donation illness in donorInfection in recipient with no other risk

Why?No testWindow period infectionEmerging infection

Window Periods

biggest component of risk of issuing an infectious component relates to window period

very recent infections in seroconverting donors could be missed

hepatitis B of most concern : long window period/ highest residual risk

Marker Risk (per million)

WP (days)

HBV 1: 2.2 38.3

HCV 1: 39.0 4

HIV 1: 5.9 9

Expect to miss 1 HBV/year, 1 HCV every 16.7 years and 1 HIV every 2.6 years.

Investigation of suspected TTIs

Viral (often chronic infections): May be long lag time between transfusion and diagnosis/reporting.Where there are no other known risk factors, the case is reported to clinical team at NHSBT for investigation. Re-testing of archive or subsequent samples from the donor may occur.

If possible molecular typing to prove the donor and recipient viruses are indistinguishable

Not TTI? Non-specific reactions/ Passive transfer: Parker S et al BMC Infectious Diseases. 2014:14; 99 Case report: passive transfer of hepatitis B antibodies from intravenous immunoglobulin.

What constitutes a TTI? SHOT definition

A report is classified as TTI if, following investigation:

The recipient had evidence of infection post-transfusion, and there was no evidence of infection prior to transfusion and no evidence of an alternative source of infection;

and either:At least one component received by the infected recipient was donated by a donor who had evidence of the same transmissible infection,

or:At least one component received by the infected recipient was shown to contain the agent of infection.

What is transmitted?

2005 hepatitis A and hepatitis B transmission

HAV-post-donation report/HBV early acute infection (pre-NAT)

2011 hepatitis B transmission

Things we test for and things we don t

2012/13 Parvovirus B19, HEV, HBV

B19, circulating in community

Hepatitis E genotype 3 Contaminated food

Things we don t routinely test for: hepatitis E

Widespread zoonosis, universally present in pigs

Understanding of HEV infections in England and Wales has changed

high rate of asymptomatic infectionsestimated 60 000 HEV infections/year in England and Wales

high seroprevalence: antibody positive rates of ~13%molecular characterisation studies indicate a genotype 3 virus

HEV and blood safety?

Blood components and the immunosuppressed population

Evidence of HEV turnover in blood donors in Europe

Post transfusion hepatitis linked to HEV has been reported from several countries including the UK

SE England study: Lancet

9382 minipools tested (x24) = 225,168 individual donations

78 HEV RNA repeat reactive (positive) donations

= 0.03% of donations HEV RNA positive

= 1:2900 donations HEV RNA positive

Hewitt PE, Ijaz S et al Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 2014:15;384:1766-73

Outcome in HEV infected recipients

immunocompetent infected recipients generally cleared infection rapidlyimmunosuppressed infected recipients exhibited prolonged viraemia of 4 to 35 weeks one immunosuppressed recipient treated successfully with Ribavirin in between cycles of chemotherapy, two cleared on reduction of immunosuppressionsome recipients did not become infected when expected to be so: ?? protective role of other transfused components with HEV antibodies

Do we need to test?

SaBTO working group considering impact of HEV on blood, tissues and organs

Report later in 2015 with recommendation to DH

Watch this space .

Bacterial v viral infections

Bacterial Viral

Time to report Hours-days May be years

Symptoms Usually acute May not be recognised

Outcome Serious morbidity/fatal May clear or become chronic

Reported after hospital discharge

Rarely Often

Risk reduction

In recent years bacteria main cause of TTIsStaphylococcus aureusStreptococcus pneumoniaePseudomonas spp.

Number of risk reduction measuresDonor selectionSkin cleansingDiversion pouchIPC

Bacterial screening

Bacterial screening of all platelets

Sample taken after a minimum hold of 36 hours

Released after 6 hours on BacTAlert

Bottles remain on machine until end of shelf-life or until they go ping i.e. initial reactive

Slow growing bugs may result in an initial reactive post issue: recall/transfusion

Recall

All initial reactives are recalled

Do not know if reaction is real at this point

Bottles and packs returned for testing

Not all will be positive for growth

But any patient adverse events should be reported

Does the current method work?

Type Number of packs

Initial reactive(%)

Confirmed positive (%)

Indeterminate positive (%)

Apheresis 771785 3441 (0.45) 159 (0.02) 280 (0.04)

Pool 177236 575 (0.32) 123 (0.07) 111 (0.06)

False negatives-not initial reactive by end of platelet shelf-life

2 packs September 2013 Staphylococcus aureus- not transfused

1 pack May 2014 Staphylococcus aureus- not transfused

Number of packs screened between Feb 2011 and Sept 2014

Numbers and type of organisms isolated on bacterial screening Jan-Dec 2013 (Apheresis)

0

10

20

30

40

50

60

70

GPRCNS

S. sacc

S. aur

eus

oral

strp

S. pne

u

oro-

phar

yn gut

envir

o

Bacterium

Nu

mb

ers

AphCP

AphIP

Numbers and type of organisms isolated on bacterial screening Jan -Dec 2013 (Pool)

0

5

10

15

20

25

GPRCNS

S. sacc

S. aur

eus

oral

strp

S. pne

u

oro-

phar

yn gut

envir

o

Bacterium

Nu

mb

er PoolCP

PoolIPMaximum growth time

Propionibacteria 138 hrs

S. aureus 12 hrs

S. pneumoniae 14 hrs

E. coli 10 hrs

Potential sources of contamination

DonorVenepuncture siteBloodstreamOral cavityGut

EnvironmentalSamplingComponent processing

Likely source of organisms

Skin

Failure of cleansing e.g. Staphylococcus aureus

Follicles/deeper layers anaerobes e.g. Propionibacteria

Transient bacteraemia

Gut e.g. E. coli, Streptococcus bovis

Oropharynx e.g. Streptococcus oralis, S. pneumoniae

Gut flora

Streptococcus bovis

Ca colon

non-malignant conditions of gut

E. coli

Part of normal microflora of the gut

Listeria monocytogenes

Pates, cheeses, poor outcome in immunosuppressed

? Carriage in healthy individuals

Near-missFirst known bacterial screening miss reported by NHSBT since screening began September 2013 Two apheresis platelet packs-one donorIssued to two separate hospitalsClumps observed in one packStaphylococcus aureus isolated from both packs

0

1

2

3

4

5

6

7

1996

-97

1997

-98

1998

-99

1999

-00

2000

-01

2000

-02 (

15 m

onth

s)20

0320

0420

0520

0620

0720

0820

0920

1020

11

Year of report

Nu

mb

er o

f In

cid

ents

Red Cells

Platelets

Confirmed TTIs platelets v red cells(SHOT report)

SaBTO review 2013

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/324354/SaBTO_platelets_report.pdf

Source: Public Health England

Summary

Risk of a TTI is smallDonor selection, testing and processing decrease the

riskNeed for vigilanceSuspected TTIs should be reported to NHSBTSurveillance informs current policies

Acknowledgments

NHSBT/HPA Epidemiology teamColleagues in Transfusion Microbiology