T. cruzi Incidence Study in Blood Donors and its Implications for Selective Testing: Study Results Susan L. Stramer, PhD American Red Cross BPAC Aug 2,

T. cruzi Incidence Study in Blood Donors and its Implications for Selective Testing: Study Results

Susan L. Stramer, PhDAmerican Red Cross

BPAC Aug 2, 2011

1

Acknowledgements

• ARC – Rebecca Townsend– Ed Notari– Roger Dodd– Jaye Brodsky

• Community Blood Centers of FL– Bruce Lenes– Sharon Edie– Angelica Lynn

• BSI – Brian Custer– Hany Kamel– Mike Busch

2

Major Points

• No observed incidence• Observe low level reactivity

– False positivity– Remote prior infections

• < 1% observed rate of transfusion transmissions

• Retesting policy adds no value– Complex and resource intensive

Background• The Ortho T. cruzi EIA (Ab) is used for donor screening

– ARC and BSI implemented “universal testing” Jan 29, 2007• Repeat reactive (RR) donations are further tested using a

laboratory-derived test (LDT) RIPA (Quest Diagnostics) • RIPA-pos donors are considered confirmed

– whether at index, repeat of independent index sample or at donor follow-up

• Donors of RR donations are followed and tested by EIA/RIPA– RIPA pos donors also tested by parasitologic tests

• Hemoculture (HC) and PCR – RR donors are also asked to respond to a detailed

survey regarding demographics and risk factors• True pos “cases” and false pos “controls”

4

Retest Algorithm for T. cruzi Ab RR (Ortho EIA) Donors Independent Index or Donor follow-up (F/U) samples

Sample Type Licensed Ortho EIAInterpretation

RIPA Performed (Yes/No)

If RIPA Negative or Indeterminate:

Independent Index or Follow-up Repeat Reactive Yes

Independent Index or Follow-up Nonreactive No

If RIPA Positive:

Independent Index or Follow-up

Repeat Reactive Yes

Independent Index or Follow-up

Nonreactive Yes

5

PRISM added to algorithm following licensure (April 2010)

Background• Due to low rate of transfusion transmission identified by

lookback, and donor risk being remote (22-mo experience), selective T. cruzi Ab testing implemented by all ARC and BSI regions except those included in the “Incidence Study”– 8/10/09 ARC– 4/1/10 BSI– 1X nonreactive test result qualifies the donor for all future donations

• Regions having the highest prevalence in the Southwestern and South Central portion of the US (5-fold above “system”) remained on universal testing to represent “endemic travel” and “autochthonous” risk

• Assumption was that the highest prevalence sites would provide the greatest chance of observing donor incidence (if it were to occur)

• 3 ARC = S CA (Los Angeles; 006), OK/TX (049) and AR (055)

• Community Blood Centers of FL (S FL) • Central Coast UBS (CA)

6

Incidence Study Protocol

• Continue universal testing for 5 years to extend the timeframes for detection of incident infection in repeat donors in regions with presumed increased travel to endemic areas and those with the greatest likelihood of autochthonous infection– 5 million person years (pys) total– Donor observation period target a mean of 1.9 years (from

first to last donation)– Incident case = seroconverter

• Screen RR and RIPA pos with a prior donation having a low signal (S/CO < 0.5) and who has serologic progression on follow-up on EIA (S/CO > 2.0) while remaining RIPA pos; donor may be HC/PCR pos

7

Incidence Study Outcome

• Accumulate ~ 5 million pys of observation in high prevalence areas

• We chose 4 as the number of incident donors that would be acceptable during a 5-year study as comparable to other TTD residual risks– ~ 1 incident case per million pys

• The upper 95% CI for a value of 4 is ~ 10• Upper CI of 10 per 5 million pys translates to 2 per

million pys• Add 20% for risk in remainder of US (5-fold lower)• Criterion established for study: upper limit of

acceptable risk = 2.4 cases per million pys8

Incidence Study Completion• Study completed after 48 months

– 1/29/07-1/31/11• 54 months in one region, Los Angeles

– included in the IND prior to test kit licensure• No incident/seroconverting donors were identified

9

Red Cross Biomedical Services

10

35 Regions collecting in 43 states and Puerto Rico 7 Divisions 5 National Testing Laboratories

Blood Systems Collections Areas

3 CTS laboratories13 main regional areas collecting in UBS/BCP centers located in 18 states

11

Cumulative Universal Testing T. cruzi Reactive Donors by State of Residence (01/29/07 – 01/31/11)

4

514

233

56

22

116

2

17

17

69

1

3

2

8

488

2

PR

5

5

3

48

22

15

4

5

5

1

11

5

5

7

4

21

5

15

8

7

1

Total Cases

RIPA Pos RIPA Reported

Total 3975 1179 (30%) 3947

ARC + CBCF 2540 599 2540

BSI 1435* 580* 1407*

28.8 million donations screened0.014% RR rateRR from 48 states (-DE, HI)RIPA pos (30%) from 40 states (+PR, DC)

66% from FL and CA (1:5100-1:6800)Overall: 1:24,200

1

DC

1

1

1179

48 months

12

Region

# RIPA Pos Donors

48, 54*mos

# Donations Tested

IVD + IND*RIPA Pos

Prevalence

S CA (006)* 212 1,395,964 1 : 6,585

OK/TX (049) 15 391,263 1 : 26,084

AR (055) 16 452,219 1 : 28,264

CBCF 203 1,033,005 1 : 5,089

Central Coast UBS 20 365,855 1 : 18,293

Total466 (60%) 3,638,306

1 : 7,808 (4.3-fold higher)

All Other ARC+BSI 312 22,379,332 1 : 71,729

All Total 778 26,017,628 1 : 33,442

T. cruzi Seroprevalence – Universal + Selective 48 months

13

Combined Lookback Experience

Component No. Recipients Tested

No. ELISA/RIPA Pos (minus other risk factors)

ARC 48 mos

ABC 22 mos

RBC 71 81 0

Platelets 9 24 (1*), 2**

Plasma+ Cryo 20 42 0

Whole Blood 3 0 0

Unknown 7 0 0

Total Conf’d 112 147 2 (0.8% of 259 total tested)

* 1 El Salvadoran recipient rec’d random donor platelets from a Brazilian donor; both donor/recipient PCR/HC (-); likely preexisting Ab in recipient**2 apheresis platelet recipients (no other risk factors) from 2 difft dtns from an Argentine donor; both donor/recipient PCR/HC (+) 14

Combined Lookback Experience

• Risk of transfusion transmission in the US as determined by tracing prior donations from RIPA-positive donors since the initiation of widespread T. cruzi Ab testing using FDA licensed screening assays and contemporary methods of component manufacture/transfusion practice is < 1%

15

When does transfusion transmission occur; US/CanadaCase Reported # Recipients Infected

Component/Medical Condition (*immunosuppressed)

Donor/Birth Country/Yrs US/Canada

Donor Pos Test Results

(when available)

Kessler et al.NYC 2010

2 – platelets (US) Argentina 40 yrs

EIA S/CO 5-6; RIPA+; PCR/HC+

Young et al. Rhode Island 2007

1 – platelets (US); irrad/LR’d; neuroblastoma*

Bolivia 17 yrs

1:256 IFA (13 weeks post dtn)

Lane et al. Manitoba 2000

1 - 299 platelets/8 RBC units (Canada); prolymphocytic leukemia*

Germany (born) Paraguay (child)

2 difft EIAs/RIPA+

Leiby et al.Miami 1999

1 – platelets (US); multiple myeloma*

Chile 33 yrs

EIA S/CO/RIPA+; PCR/HC+; donor & recip linked

Cimo et al. Houston 1993

1 - >500 units (US); colon cancer*

No donor identified

Grant et al. NYC 1989

1 – platelets (US); Hodgkin’s disease*

Bolivia 16 yrs

1:512 IFA

Nickerson et al Manitoba 1989

1 – platelets (Canada); acute lymphocytic leukemia*

Paraguay 20 yrs

> 1:2000 ELISA

Geiseler et al Southern CA 1987

1 – blood products (US/endemic travel); acute leukemia*

Likely father (Mexico)

1:128 IFA

16

Course of Infection in Platelet RecipientLeiby et al, NEJM, 1999; 341(16):1237-1239

Days Post-transfusion

Sig

nal

/Cu

toff

(s/

co)

0 20 40 60 80 100 120 140 160

PCR & HC positive

0

1

2

3

17

Person-Time (Donor Observation Period) Calculations

• All donors with > 2 T. cruzi Ab screened donations selected during 48 months (54 months Los Angeles)

• Time from first => last donation for each donor calculated (observation period); expressed as pys

• Calculated pys separately for each analysis– Mean observation period – Total observation period– Graphs used person months to show groups of donors

within specific observation times• Incidence and Exact binary upper and lower 95%

confidence limits (UCL, LCL) calculated

18

Risk/SiteNumber

of Donors

Mean Observation Period (pys)

Incident Cases 95%CL

(LCL;UCL)per million pys

Total Observation Period (pys)

Travel Risk

ARC Los Angeles (006) [54 months] 244,498 1.696 0 (0; 8.9) 414,578

UBS Central Coast (CC, 034)[48 months] 49,591 1.639 0 (0; 45.4) 81,293

Subtotal 294,089 1.686 0 (0; 7.4) 495,871

Autochthonous Risk

ARC Southwest (OK/TX; 049) 59,045 1.420 0 (0; 44.0) 83,856

ARC Greater Ozarks (AR; 055) 74,920 1.550 0 (0; 31.8) 116,152

Subtotal ARC 133,965 1.493 0 (0; 18.4) 200,008BSI Regions (11,16,20,26 & 31; TX, AR, MS, LA)Subtotal BSI

175,611 1.468 0 (0; 14.3) 257,773

Subtotal ARC + BSI[48 months]

309,576 1.479 0 (0; 8.1) 457,781

Incidence Study Outcomes

19

Risk/Site Number of Donors

Mean Observation Period (pys)

Incident Cases 95%CL

(LCL;UCL)per million pys

Total Observation Period (pys)

Overall Risk

ARC, all donations (universal + selective) [48-54 months]

3,523,894 1.402 0 (0; 0.75) 4,941,088

BSI, all donations (universal + selective) [48 months]

698,391 1.601 0 (0; 3.3) 1,118,274

Total 4,222,285 1.435 0 (0; 0.61) 6,059,362

Extended Observation Periods

ARC all apheresis donations [48-54 months]

492,020 1.643 0 (0; 4.6) 808,313

BSI all apheresis donations [48 months]

275,963 1.790 0 (0; 7.5) 494,095

Total Apheresis 767,983 1.696 0 (0; 2.8) 1,302,408

20

Distribution of Donor Observation Time for The Chagas Incidence Study54/48 Month Study Period, 08/01/2006 to 01/31/2011

Travel Risk, Region 006 [ARC, 54 Months] & Region 034 [BSI, 48 Months]Allogeneic Donors, 14 Person-Days or Greater

0

2,500

5,000

7,500

10,000

12,500

15,000

17,500

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Cumulative Time of Observation (Months)

Nu

mb

er

of

Do

no

rs

Total Number of Donors294,089

Mean Person Years (95% CI)1.686 (1.690, 1.682)

Incidence per 100,000 PY (95% CI)0 (0.7439, 0)

Graph_Chagas_Travel_Both

21

Distribution of Donor Observation Time for The Chagas Incidence Study48 Month Study Period, 01/29/2007 to 01/31/2011

Regions 049 & 055 (ARC) and Regions 011, 016, 020, 026 & 031 (BSI)All Regions With Autochthonous Risk

0

2,500

5,000

7,500

10,000

12,500

15,000

17,500

20,000

0 4 8 12 16 20 24 28 32 36 40 44 48


Nu

mb

er

of

Do

no

rs




Graph_Chagas_Autoch_Both

22


All Regions, All Donors - Both OrganizationsAllogeneic Donors, 14 Person-Days or Greater

0

50,000

100,000

150,000

200,000

250,000

300,000

0 4 8 12 16 20 24 28 32 36 40 44 48


Nu

mb

er

of

Do

no

rs

Total Number of Donors4,222,285



Graph_Chagas_ALL_Both

----Selective testing----

23


All Regions - Both OrganizationsEach donor having one or more apheresis procedures

0

10,000

20,000

30,000

40,000

50,000

0 4 8 12 16 20 24 28 32 36 40 44 48


Nu

mb

er

of

Do

no

rs




Graph_Chagas_ALL_APH_Both

----Selective testing----

24

Possible Seroconverters Identified During Universal Testing

• 22 donors identified with nonreactive Ab tests who on subsequent donation at 41-532 days were found to be RR and RIPA pos (index, repeat independent sample or follow-up)– 21 based on Ortho EIA testing– 1 based on Abbott PRISM clinical trial

• Reactivity was inconsistent and none of these donors met the definition of an incident/ seroconverting donor

25

Course of Infection in Platelet RecipientLeiby et al, NEJM, 1999; 341(16):1237-1239

Days Post-transfusion

Sig

nal

/Cu

toff

(s/

co)

0 20 40 60 80 100 120 140 160

PCR & HC positive

0

1

2

3

26

Possible Seroconverters Identified During Universal Testing (to 8/9/09)

N=18; 13/13 PCR and 14/14 HC Negative

00.5

11.5

22.5

33.5

44.5

5

-700

-650

-600

-550

-500

-450

-400

-350

-300

-250

-200

-150

-100 -5

0 0 50 100

150

200

250

300

350

400

450

500

550

600

650

700

750

800

850

Days

S/C

O

27

Possible Seroconverters Identified by Sites Remaining on Universal Testing (from 8/10/09)

N=4; 2/2 PCR and HC Negative

00.5

11.5

22.5

33.5

44.5

5

-120

0-1

150

-110

0-1

050

-100

0-9

50-9

00-8

50-8

00-7

50-7

00-6

50-6

00-5

50-5

00-4

50-4

00-3

50-3

00-2

50-2

00-1

50-1

00 -50 0 50 100

150

200

250

300

350

400

Days

S/C

O

28

WBN

Prior DonationIndex

Collect Date

Testing Interval (days)

State

Ab ELISA S/CO

RIPAPRISM S/COIndex

PCR HCCollect Date S/CO (Index, 2nd Index, F/U)

011LK52205 3/18/07 0.983 4/28/07 41 MO 1.317*/0.038/ 1.384*/1.419 -/+/-/- 0.15 - -/-

017GN57725 2/27/07 0.835 6/7/07 100 WI 1.794*/0.455/ 0.411/0.834/0.634 +/-/+/-/- 0.06 -/-/- -/-/-

021KE29415 5/10/07 0.475 8/21/07 103 OR 1.078*/1.054*/ 1.277* -/+/- 0.05 - -

004L 96697 4/30/07 0.819 8/30/07 122 NH 1.166*/0.811/ 0.959/1.008* +/+/-/- 0.10 -/- -/-

012C 81057 7/11/07 0.802 9/5/07 56 NC 1.120*/0.737/ 0.770/0.846 +/+/-/- 0.06 -/- -/-

049GL34705 7/19/07 0.440 11/8/07 112 OK 1.035*/0.599/ 0.705/1.050* +/-/-/+ 0.06 -/- -/-

053FW61740 4/14/07 0.836 12/13/07 243 VA 1.096*/1.092* +/+ 1.22* NA NA

036FP31850 10/16/07 0.852 2/12/08 119 SC 1.114*/1.116*/ 0.830/1.003* -/+/-/- 0.16 -/- -

020FT11144 11/19/07 0.869 4/2/08 135 UT 1.021*/0.931/ 1.010* +/-/- 0.05 - -

011GZ71884 4/4/07 0.239 5/21/08 413 MO 1.492*/1.761*/ 2.960*/0.411 -/-/+/- 0.27 NA -

020FW16929 1/31/08 0.689 5/29/08 119 UT 1.333*/0.749/ 1.041/0.251/0.857 -/- /+/-/- 0.13 -/- -/-

007FM15946 4/30/08 0.371 6/23/08 54 AZ 1.291*/0.523/ 0.222/0.485 +/+/-/- 0.07 - -/-

024GY39349 5/6/08 0.230 7/19/08 74 IN 1.178*/0.839/ 1. 187/0.641/0.309 -/- /+/-/- 0.48 -/- -/-

006FP69971 2/20/07 0.915 8/5/08 532 CA 1.110*/1.100* +/- 0.72 NA NA

006GS26670 6/4/08 0.124 8/6/08 63 CA 0.116/0.095/ 0.094/0.106 +/-/-/- 1.51*/0.81 -/- -/-

022GJ11661 3/12/08 0.399 8/8/08 149 PA 1.110*/0.113 +/- 0.06 NA NA

W0368 12/16/08 0.961 4/29/09 134 FL 1.123*/0.280/ 0.346 /0.316 +/-/Ind/- 0.14 -/- -/-

038GE30113 2/10/09 0.976 5/29/09 108 IN 1.083*/0.923 +/+ 0.45 NA NA

Possible Seroconverter Cases N=18 (1/29/07-8/9/09)

* Denotes average of 3 S/CO values

Chagas Clinical Trial sample with RR PRISM at Index

Yellow highlighted S/CO = 20% elevated negative

29

Possible Seroconverter Cases N=4 (8/10/09-1/31/11)3 regions and CBCF that continued

with Universal Testing

WBN

Prior DonationIndex

Collect Date

Testing Interval (days)

State

Ab ELISA S/CO

RIPAPRISM S/COIndex

PCR HCCollect Date S/CO (Index, 2nd Index, F/U)

006GG00723 01/04/09 0.941 08/21/2009 229 CA 1.086*/1.024* -/+ 3.06* NA NA

006GX87964 05/22/09 0.994 12/09/2009 201 CA 1.083*/0.046/1.217* +/-/- 0.06 - -

006LH19583 01/26/10 0.332 06/08/2010 133 CA 1.203*/1.009*/0.522 +/+/+ 2.64* - -

006KP44769 09/02/10 0.217 09/16/2010 14 CA 1.663*/0.344/0.087 +/-/- 0.17 pend pend

* Denotes average of 3 S/CO valuesYellow highlighted S/CO = 20% elevated negative

Of 18+4: 3 “yes” responses on risk questions; all followed with no seroconversion006LH19583 born and lived in Mexico 39 yrs006GX87964 Hispanic, born in US W036809203439 born and lived in Venezuela for 10 yrs

30

T. cruzi antibody reactivityPheresis donor 006KP44769

0

0.5

1

1.5

2

2.5

3

S/C

O

Date

18 prior nonreactive donations

RR/RIPA pos donationand retesting of regional

retention sample

Follow-up collected 298 days post index

Assay cutoff

31

US-Derived T. cruzi Study (USTC) 54 eligible RR/RIPA Pos donors (48 ARC and 8 UBS); 37 enrolled

15 Defined as Concordant (CG)/22 Discordant (DG)

Vector and reservoirN=28 and N=17Vector only

PR

32

WBN

Prior Donation

RIPAPRISM S/COIndex

CDC TestingLeish IFA

Focus, USA

Collect Date

S/CO

IFAEpi lysateCDC In house

Chagatest EIArDNA

Weiner, Argentina

TESATrypo lysate

bioMx, France

011LK52205 3/18/07 0.983 -/+/-/- 0.15 Neg Neg Neg Neg

017GN57725 2/27/07 0.835 +/-/+/-/- 0.06 Neg Neg Neg Neg

004L 96697 4/30/07 0.819 +/+/-/- 0.10 Neg Neg Neg Neg

012C 81057 7/11/07 0.802 +/+/-/- 0.06 Neg Neg Neg Neg

049GL34705 7/19/07 0.440 +/-/-/+ 0.06 Neg Neg Neg Neg

020FW16929 1/31/08 0.689 -/- /+/-/- 0.13 Neg Neg Neg Neg

007FM15946 4/30/08 0.371 +/+/-/- 0.07 Neg Neg Neg Neg

024GY39349 5/6/08 0.230 -/- /+/-/- 0.48 Neg Neg Neg Neg

006GS26670 6/4/08 0.124 +/-/-/-1.51* /0.81

Neg Neg Neg Neg

Possible Seroconverter Cases N=18 (1/29/07-8/9/09) enrolled in USTC

Chagas Clinical Trial sample with RR PRISM at IndexYellow highlighted S/CO = 20% elevated negative 33

USTC Testing Results for the Discordant Group (DG); N=22ID Index Ortho EIA No. RR Ortho/ No. pos RIPA/ IFA titer Wiener EIA TESA PRISM Mean

Mean S/CO No. tested No. tested 1:X S/CO

DG1 3.4 3/4 1/3 ≤16 NEG NEG 0.21

DG2 2.8 4/4 1/4 ≤16 NEG NEG 0.06

DG3 2.5 4/5 1/4 ≤16 NEG NEG 0.15

DG4 1.9 5/5 5/5 ≤16 NEG NEG 0.42

DG5 1.8 3/4 1/4 ≤16 NEG NEG 0.17

DG6 1.8 1/5 2/5 ≤16 NEG NEG 0.06

DG7 1.7 2/4 1/4 ≤16 NEG NEG 0.10

DG8 1.4 3/4 2/4 ≤16 NEG NEG 0.11

DG9 1.3 2/5 1/4 ≤16 NEG NEG 0.13

DG10 1.3 3/4 1/4 ≤16 NEG NEG 0.15

DG11 1.3 1/4 2/4 ≤16 NEG NEG 0.07

DG12 1.3 1/4 2/4 ≤16 NEG NEG 0.15

DG13 1.2 4/5 1/5 ≤16 NEG NEG 0.07

DG14 1.2 3/5 2/4 ≤16 NEG NEG 0.17

DG15 1.2 2/5 1/5 ≤16 NEG NEG 0.48

DG16 1.2 2/4 2/4 ≤16 NEG NEG 0.10

DG17 1.2 3/4 1/3 ≤16 NEG NEG N/A

DG18 1.1 1/4 2/4 ≤16 NEG NEG 0.06

DG19 1.1 1/5 1/5 ≤16 NEG NEG 0.08

DG20 1.0 2/4 2/4 ≤16 NEG NEG 0.06

DG21 1.0 1/5 1/5 ≤16 NEG NEG 0.05

DG22 0.1 0/4 1/4 ≤16 NEG NEG 0.81 34

Rate of Possible Seroconverters: Universal Testing ARC + CBCF

Testing Period

Time Frame

Total Donations

No. Frequency

Universal Testing

1/29/07-8/9/09; 31 mos

17,568,120 18 1/976,007*

Cont’d Universal Testing

8/10/09-1/31/11; 17 mos

1,414,402 4 1/353,601*

TOTAL 48 months

18,982,522 22 1/862,842

* NS; p = 0.10 Chi square and Exact measures mid-P (2-tail) 35

Assay VariabilityBiologic (test component or other agent, remote prior

infection)/Analytic (cutoff) • Donor follow-up of 3 donor populations derived from

246 RR/RIPA Pos ARC donors enrolled in follow-up during 48 months (651 total RIPA pos)– N=174 Consistent RR/RIPA Pos– N=57 Inconsistent RR/RIPA Pos

• Index Ortho EIA RR; RIPA pos index or follow up

– N=22 Possible Seroconverters with 16 donors followed (15 Ortho EIA/1 Abbott PRISM triggered)

• Demographic analysis of 3 populations• Analysis of Ortho EIA cutoff values for 3 populations• Relationship of Ab S/CO values with PCR positivity

– Higher S/CO values correlate with PCR positivity36

0

10

20

30

40

0 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8

Nu

mb

er

of

Do

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rs

S/CO Value

Sample description NIndex Ortho EIA Median

S/CO

Index Abbott PRISM Median

S/CO

Consistent EIA/RIPA (+) 174 4.79 5.55

Inconsistent EIA/RIPA (+) 57 1.39 1.25

Possible Seroconverters inconsistently EIA/RIPA (+)

21 (15) 1.17 0.14

Distribution of T. cruzi RIPA-Positive Donation S/CO Values ARC Donors Participating in Follow-up (n=246)

Mean Ortho EIA Test-of-Record Results

Mean follow-up 76 days (2 - 1083)



37

Distribution of T. cruzi RIPA-Positive Donation S/CO Values ARC Donors Participating in Follow-up

Mean Ortho EIA Test-of-Record Results

Jaye’s Box and Whisker graph4.79

1.39 1.17

N = 174* N = 57 N = 15*p < 0.0001 Wilcoxon

Rank Sums

38

% PCR + 30 4 0 HC + 8 0 0

Variable No. (%) Consistent

(N=156) “AA”

No. (%) Inconsistent (N=50) “BB”

No. (%) Possible Seroconverters

(N=16) “CC”

Born in endemic country 139 (89) 31 (62)*** ***2 (13)*

Lived in endemic country > 1 yr 142 (91) 31 (62)*** ***2 (13)*

Time in endemic country >1 yr Mean 20 yrs (1-51) Mean 21 yrs (1-39) (10 and 39)

Mother/maternal grandmother born in an endemic country 141 (90) 32 (64)*** ***3 (19)*

Hispanic 143 (92) 34 (68)*** ***3 (19)*

House dirt floors/walls 95/142 (67) 27/36 (75) 1/3 (33)

Lived in a rural area 102/142 (72) 29/36 (81) 2/3 (67)

House thatched roof 40/142 (28) 7/36 (19) 0 (0)

Age Mean 44yrs (16-82)

Mean 43yrs (17-80)

Mean 37yrs (17-74)

Male 67 (43) 30 (60) 10 (63)

Female 89 (57) 20 (40) 6 (37)

Risk Factors/Demographics: RIPA-Pos Donors – 48 months

Chi-square with Yates correction; *p<0.01;***p < 0.0001;3 “yes” no seroconversion39

0

5000

10000

15000

20000

25000

30000

35000

40000

0.2

40

0.2

52

0.2

64

0.2

76

0.2

88

0.3

00

0.3

12

0.3

24

0.3

36

0.3

48

0.3

60

0.3

72

0.3

84

0.3

96

0.4

08

0.4

20

0.4

32

0.4

44

0.4

56

0.4

68

0.4

80

0.4

92

0.5

04

0.5

16

0.5

28

0.5

40

0.5

52

0.5

64

0.5

76

0.5

88

0.6

00

0.6

12

0.6

24

0.6

36

0.6

48

0.6

60

0.6

72

0.6

84

Cutoff midpoint

Fre

qu

en

cy

Ortho Assay Variability as defined by the CutoffCutoff = PC mean [0.425]; PC range = OD ≥ 0.300, ≤ 1.800

Group #Runs/#Samples Cutoff OD Mean% Runs <0.338

Mean

All 2007-2010 71,117 0.338 50

Consistent 338 / 174 0.344 41

Inconsistent 111 / 57 0.334 57

Possible Seroconverters 30 / 15 0.328 60

Acceptable Cutoff Range:0.1275 – 0.705

40

T. cruzi Ab reactivity (EIA) correlates with PCR positivity among seroreactive donors in Brazil, Honduras, US

Sabino et al., accepted 2011 AABB Annual Mtg

p<0.005p<0.001 p<0.0001

6.57

5.78

6.33

4.27

5.50

3.56

9 40 45 19 16 81N= 41

Impact of Retesting after 2 or 5 Years• 2005 donor cohort (~2.7 million donors) followed from first to last donation• 9-year donation data to model retest volume (~60 million donations) for a 2- or 5-year retest policy

42

Determination of Repeat Donation Patterns for ARC Donors in CY2005

• All donors with an initial donation in CY2005 who had subsequent donations through CY2010 included

• Time from first => last donation calculated• Plotted the number of donors within the

2005 cohort (2,678,057) who continued to donate (i.e., not yet had their last donation within the study period)

43

ARC CY2005 Donor Return PatternsN = 2,678,057

25% (0.7 Million)

43% (1.1 Million)

55% (1.5 Million)

66% (1.8 Million)

80% (2.1 Million)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 12 24 36 48 60 72

Months

Pe

rce

nt

of

Do

no

rs R

em

ain

ing

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

Nu

mb

er

of

Do

no

rs R

em

ain

ing

Percent

Donors

44

Application of a 2-Year Retesting Policy on Nine Years of ARC DonationsN = 59,674,858

5th Test

4th Test 4th Test 4th Test3rd Test 3rd Test

3rd Test 3rd Test 3rd Test

2nd Test

2nd Test

2nd Test2nd Test

2nd Test2nd Test 2nd Test

1st Test

1st Test

1st Test

1st Test

1st Test1st Test

1st Test1st Test

1st Test

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

3,500,000

4,000,000

4,500,000

2002 2003 2004 2005 2006 2007 2008 2009 2010

Calendar Year

Do

na

tio

ns

Te

ste

d

36,688,648 Untested donations15,850,682 1st Test donations 7,135,528 Retest donations

45

Application of a 5-Year Retesting Policy on Nine Years of ARC DonationsN = 59,674,858

2nd Test2nd Test

2nd Test2nd Test

1st Test

1st Test

1st Test1st Test

1st Test

1st Test

1st Test

1st Test

1st Test

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

1st TestFirst Time

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

3,500,000

4,000,000

4,500,000

2002 2003 2004 2005 2006 2007 2008 2009 2010

Calendar Year

Do

na

tio

ns

Te

ste

d

41,773,568 Untested donations15,850,682 1st Test donations 2,050,608 Retest donations

46

Summary• Ongoing 1-time testing to qualify a donor for repeat donation

is “safe” as evidenced by: – Zero observed incidence in the 4-year “Incidence Study”

• 6 million plus pys of observation• 4.22 million donors (mean obs time = 1.435 pys)

– Upper 95% confidence value (0.61/million pys) yielded risk of incidence lower than that of other current infectious diseases

– < 1% obs’d occurrence of transfusion transmission• Risk greatest in donors with high S/CO values,

consistently RIPA pos and PCR/HC pos • Low frequency of donors identified during universal testing

from ARC + CBCF with inconsistent reactivity who were not seroconverters

– 22/~19 million donations or 1/900,000– Biologic and analytic false positives, remote prior

infection?

47

Summary

• Retesting test-negative donors after 2 or 5 years adds no value relative to the low (no) risk of incidence and infrequent occurrence of transfusion transmission– Implementation of such systems would be a

burden to blood centers requiring significant resources• Anywhere from 500,000 to 1 million

additional tests per year for the ARC; 2x for the US

• Competes/may prevent the implementation of other other safety initiatives–e.g., Babesia

48

Conclusion• A selective testing strategy based on qualifying a donor by a single negative donation has high sensitivity and has significantly reduced the amount of testing required without compromising recipient safety

49

Documents

T. cruzi Incidence Study in Blood Donors and its Implications for Selective Testing: Study Results Susan L. Stramer, PhD American Red Cross BPAC Aug 2,