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Issues Regarding Qualification/Implementation of Issues Regarding Qualification/Implementation of an Antibody Test for Trypanosoma cruzian Antibody Test for Trypanosoma cruzi

Susan L. Stramer, PhDSusan L. Stramer, PhD

American Red CrossAmerican Red Cross

Blood Products Advisory Committee MeetingBlood Products Advisory Committee Meeting

April 26, 2007April 26, 2007

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OutlineOutline Clinical study design and resultsClinical study design and results

– 8/28/06 to 1/28/078/28/06 to 1/28/07– 3 regions (West Division); SoCal, NoCal, AZ3 regions (West Division); SoCal, NoCal, AZ– MMWR 2/23/07; 56 (07):141-143MMWR 2/23/07; 56 (07):141-143

Implementation: AABB Association Bulletin #06-08Implementation: AABB Association Bulletin #06-08 IVD results 1/29/07-4/17/07; approx 65% collected blood USIVD results 1/29/07-4/17/07; approx 65% collected blood US

– ARC, UBS, 15 other blood centers and >50 hospitalsARC, UBS, 15 other blood centers and >50 hospitals– Distribution in US and accuracy of predictionsDistribution in US and accuracy of predictions

Test performanceTest performance– ELISA, RIPA, ELISA, RIPA, T. cruziT. cruzi IFA, IFA, LeishmaniaLeishmania IFA, “Special Protocol” IFA, “Special Protocol”

Lookback resultsLookback results Donor demographicsDonor demographics

– Risk factorsRisk factors– Possible autochthonous cases (indigenous, native)Possible autochthonous cases (indigenous, native)

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Chagas Protocol/AssumptionsChagas Protocol/Assumptions FDA request of Ortho to expand clinical studies to include areas FDA request of Ortho to expand clinical studies to include areas

where where T. cruziT. cruzi antibody prevalence previously documented antibody prevalence previously documented– Pivotal clinical trial yield 0 conf’d pos (of 40,665 tested); Pivotal clinical trial yield 0 conf’d pos (of 40,665 tested);

99.998% specificity (PI) 99.998% specificity (PI) – 100,000 donations defined the study100,000 donations defined the study– Testing would continue through test licensure and implementationTesting would continue through test licensure and implementation– SoCal, NoCal and AZ (West ARC Division)SoCal, NoCal and AZ (West ARC Division)

• FDA requirements for donor informed consentFDA requirements for donor informed consent– Use of an information sheet with signature on BDR Use of an information sheet with signature on BDR

acknowledging receipt not allowedacknowledging receipt not allowed– Specific signature Specific signature and dateand date required on info sheet; matched required on info sheet; matched

to tubes that were testedto tubes that were tested• Due to these requirements, other blood centers declinedDue to these requirements, other blood centers declined

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ARC Prevalence Study T. cruzi Results ARC Prevalence Study T. cruzi Results 8/28/06-1/28/078/28/06-1/28/07

All sites All sites SoCalSoCal ArizonaArizona NoCalNoCal

Total Total Attempted Attempted

DonorsDonors

189,828189,828 127,053127,053 26,60126,601 36,17436,174

Total Total TestedTested

148,969148,969 95,66295,662 23,98123,981 29,32629,326

Total RRTotal RR

ConfirmedConfirmed

63 (1:2365)63 (1:2365)

32 (1:4655)32 (1:4655)

50 (1:1913)50 (1:1913)

25 (1:3827)25 (1:3827)

4 (1:5995)4 (1:5995)

2 (1:11,990)2 (1:11,990)

9 (1:3258)9 (1:3258)

5 (1:5865)5 (1:5865)

Total (%) Total (%) RefusalsRefusals

40,859 40,859 (21.5%)(21.5%)

31,391 31,391 (24.7%)(24.7%)

2620 2620 (9.8%)(9.8%)

6848 6848 (18.9%)(18.9%)

40,859 refusals/detection rate of 1:4655 = 9 undetected donors!

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The prevalence of infection with T. cruzi in the The prevalence of infection with T. cruzi in the US varies by region and might now be higher US varies by region and might now be higher

than previously thought, especially in geographic than previously thought, especially in geographic areas such as Los Angeles County, where a areas such as Los Angeles County, where a

substantial proportion of blood and organ donors substantial proportion of blood and organ donors have emigrated from Chagas-endemic countries.have emigrated from Chagas-endemic countries.

MMWR 55 (29); 2006MMWR 55 (29); 2006

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ImplementationImplementation According to AABB Assn Bull #06-08According to AABB Assn Bull #06-08

– Collaboration with the CDC and FDACollaboration with the CDC and FDA Component mgmtComponent mgmt

– Components from RR donors quarantined/withdrawn from Components from RR donors quarantined/withdrawn from the market (3 calendar days)the market (3 calendar days)• Index Index • Prior in-date donations Prior in-date donations

– As long as electronic records existAs long as electronic records exist– Recipient tracingRecipient tracing

– Autologous unit release with approval of auto donor’s Autologous unit release with approval of auto donor’s referring physicianreferring physician

– Inventory testing (in-house or distributed) not Inventory testing (in-house or distributed) not recommended; each facility assess riskrecommended; each facility assess risk

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ImplementationImplementation Donor mgmtDonor mgmt

– RRs notified/deferredRRs notified/deferred– Supplemental testing encouraged, although no FDA licensed Supplemental testing encouraged, although no FDA licensed

confirmatory/supplemental test exists confirmatory/supplemental test exists • RIPA most sensitive test, however not 100%RIPA most sensitive test, however not 100%

– Leishmania Leishmania testing on supplemental test unconfirmed; no mention testing on supplemental test unconfirmed; no mention PlasmodiumPlasmodium or or Paracoccidiodes braziliensusParacoccidiodes braziliensus

– Donor counseling including donor follow-up studies encouragedDonor counseling including donor follow-up studies encouraged– No donor reentryNo donor reentry– Refer supplemental test positive donors to knowledgeable physicianRefer supplemental test positive donors to knowledgeable physician

• Referrals from personal physician, blood center, Am Assoc Tropical Med or Referrals from personal physician, blood center, Am Assoc Tropical Med or CDC CDC

– Recipient tracing from supplemental test positive donorsRecipient tracing from supplemental test positive donors• ““Licensed test for Ab detection has suitable performance characteristics for Licensed test for Ab detection has suitable performance characteristics for

blood donor screening and as such may be useful in testing of the above blood donor screening and as such may be useful in testing of the above individuals.”individuals.”

COI and Component LabelsCOI and Component Labels– Component tested by a licensed test and the results are negative/nonreactiveComponent tested by a licensed test and the results are negative/nonreactive

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Models for Testing/ImplementationModels for Testing/Implementation UniversalUniversal Immunosuppressed patientsImmunosuppressed patients

– Puts burden on hospitals to identify correct units for recipients at highest riskPuts burden on hospitals to identify correct units for recipients at highest risk Geographic modelsGeographic models

– By US census data/WHO seroprevalence by countryBy US census data/WHO seroprevalence by country Test one-time-only per donor where only new donors are tested; Test one-time-only per donor where only new donors are tested;

repeat donors are questioned re risk and only “yes” responses are repeat donors are questioned re risk and only “yes” responses are testedtested– Assumes donor understands the questions, questions may be culturally Assumes donor understands the questions, questions may be culturally

sensitive, assumes no autochthonous risksensitive, assumes no autochthonous risk– Must be validated; each positive requires knowledge of risk and when it Must be validated; each positive requires knowledge of risk and when it

occurredoccurred– Logistically complex relative to sample tracking and component managementLogistically complex relative to sample tracking and component management– Financial benefit has not been validatedFinancial benefit has not been validated– Confusing message to test kit developersConfusing message to test kit developers

T. cruzi Reactive Donors by State of Residence (01/29/07 – 04/17/07)

3

58

56

612

15

10

2

4

3

6

6

4

2

3

37

4

PR

Total RR Donors

RIPA Pos RIPA Reported

ARC 213 41 191

Blood Systems 52 7 (2) 29 (4)

1

3

2

2

4

8

6

2

7

7

1 3

2

5

3

4

1

1

1

3

3

2

3

1

1

Nos. indicate 265 RR donors by state;no RR donors or testing not occurringin 6 states;48 confirmed pos (+2) in 17 states:19 CA, 11 FL, 3 MD, 2 NY, UT, VA;1 AR, CT, GA, MA, MT, NC, NJ, ORTN, WA, (AZ)

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RR donations reported to the AABB; 4/24/077 facilities reporting; 4 sites with RR donors272 total RR

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Confirmed pos reported to the AABB website

Of 228 = 21.5%

Repeat Reactive Donors by Week (N = 218) ARC only

0

5

10

15

20

25

30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Testing Week (Start 01/29/2007)

Case

s

RIPA pos (N = 41) RIPA neg/pending (N = 177)

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Do the states in which confirmed positive donors Do the states in which confirmed positive donors agree with models based on immigration?agree with models based on immigration?

N.J. - N.Y. Metro

Washington, D.C.

L.A. County

Based on immigration and test positive rates for endemic countries

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QUESTRIPAIndex Sample

Plasma or Retention Sample All Follow-up

1. T. cruzi Ab 2. HL RIPA

3. Leishmania Ab IFA

Plasma or Retention Sample

1. T. cruzi Ab 2. HL RIPA

Positive

3. PCR(Unprocessed EDTA*)

4. Hemoculture(Heparin*)

1. T. cruzi Ab

2. HL RIPA5.

LeishmaniaAb IFA

Send

Do NOTsend

Reactive

Non-Reactive

Negative /Indeterminate

(or Grey ZoneIndeterminate)

* = If these sample types are received

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Test PerformanceTest Performance Clinical trial (8/28/06-1/28/07)Clinical trial (8/28/06-1/28/07)

– PPV = PPV = 32 RIPA32 RIPA pospos/63 RR=/63 RR=51%51%; pos in 2 states; pos in 2 states– RR rate = 63/148,969 = 0.042%RR rate = 63/148,969 = 0.042%– Prevalence = 32/148,969 = Prevalence = 32/148,969 = 1:46551:4655– Specificity = 148,906 test neg/148,906+31 false pos = Specificity = 148,906 test neg/148,906+31 false pos = 99.979%99.979%

• 99.997%99.997% in PI in PI Nationwide screening (1/29/07-4/17/07)Nationwide screening (1/29/07-4/17/07)

– PPV = PPV = 50 RIPA50 RIPA pospos/224 RR RIPA tested = /224 RR RIPA tested = 22%22%; pos in 17 states; pos in 17 states• 30 of 50 (60%) RIPA pos from 2 states (S CA, FL)30 of 50 (60%) RIPA pos from 2 states (S CA, FL)

– RR rate = 265 RRs (213 ARC + 52 BSL)/1,757,800 donations = 0.015%RR rate = 265 RRs (213 ARC + 52 BSL)/1,757,800 donations = 0.015%– Projected prevalence based on 22% PPV of RIPA tested = Projected prevalence based on 22% PPV of RIPA tested = 1:30,1501:30,150– Specificity (ARC) first week = 124,934 test neg/124,934+28 false pos = Specificity (ARC) first week = 124,934 test neg/124,934+28 false pos =

99.978%99.978% (6 pos) (6 pos) Overall prevalence = Overall prevalence = 1:21,1001:21,100, and , and 27%27% rate of RIPA positivity rate of RIPA positivity

Index T. cruzi Samples with RIPA Results (N = 254)

0102030405060708090

100110120130140150

0.8 1 2 3 4 5 6 7 T. cruzi Ab S/CO Values

Fre

qu

ency

Samples (ARC/BSL)

N % Mean S/CO S/CO Range

RIPA Positive 73 29% 3.45 0.93 – 7.72

RIPA Negative 181 71% 1.42 0.82 – 3.89

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Variability of ELISA/RIPAVariability of ELISA/RIPA 3 samples in 10% negative gray zone that were RIPA pos3 samples in 10% negative gray zone that were RIPA pos 2 samples +/- RIPA (index serum pos/neg in ret’d plasma)2 samples +/- RIPA (index serum pos/neg in ret’d plasma) Samples ELISA reactive @ index, nonrx ret’d plasma, reactive in f/uSamples ELISA reactive @ index, nonrx ret’d plasma, reactive in f/u

Index ELISAIndex ELISA Plasma ELISAPlasma ELISA Follow up ELISAFollow up ELISA RIPA RIPA indexindex

RIPA RIPA plasmaplasma

RIPA RIPA f/uf/u

0.96, 0.96, 1.2, 1.11.2, 1.1 0.850.85 n/an/a pospos pospos n/an/a

0.93, 0.93, 1.0,1.0, 0.98 0.98 n/an/a 0.96,0.99, 0.990.96,0.99, 0.99 pospos n/an/a pospos

0.98,0.98,1.05, 1.01.05, 1.0 0.230.23 n/an/a pospos negneg n/an/a

1.0, 1.1, 1.11.0, 1.1, 1.1 0.340.34 n/an/a pospos negneg n/an/a

1.2, 1.3, 1.41.2, 1.3, 1.4 0.720.72 1.43, 1.39, 1.431.43, 1.39, 1.43 pospos pospos pospos

94% RIPA pos concordance = 30 ret’d plasma/32 index serum

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Retesting Retrieved Frozen PlasmaRetesting Retrieved Frozen Plasma 51 confirmed pos donors by single to multiple RIPA => 51 confirmed pos donors by single to multiple RIPA =>

retested using ELISA or other research test; 14-31% of low retested using ELISA or other research test; 14-31% of low level reactivity is lost; overall 67-84% reactivity retainedlevel reactivity is lost; overall 67-84% reactivity retained

Retrieved Plasma ResultsRetrieved Plasma Results

Serum Serum

++ -- TotalTotal ++ -- TotalTotal

++ 3434 15 15 (31%)(31%)

4949 4242 7 7 (14%)(14%)

4949

-- 00 22 22 11 11 22TotalTotal 34 34

(67%)(67%)1717 5151 43 43

(84%)(84%)88 5151

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Confirmatory: RIPA vs IFAConfirmatory: RIPA vs IFA 54 RR samples (from which 54 RR samples (from which

plasma units available for plasma units available for further testing) from the IND further testing) from the IND study were sent to Focus for study were sent to Focus for IFA and titers if IFA pos IFA and titers if IFA pos (encouragement of S. Wendel)(encouragement of S. Wendel)– 24 (44.4%) RIPA pos; 11 24 (44.4%) RIPA pos; 11

IFA pos (20.4%)IFA pos (20.4%)– 16 discordant16 discordant

• 14 IFA-/RIPA +14 IFA-/RIPA +• 2 IFA+/RIPA-2 IFA+/RIPA-

– Overall agreementOverall agreement• 38/54=70.4%38/54=70.4%

Index Index ELISAELISA

ELISA ELISA (retr’d (retr’d

plasma)plasma)

RIPA RIPA (x2)(x2)

T. cruziT. cruzi IgG IFA IgG IFA

POSPOS

4.34.3 5.25.2 POSPOS 1:161:16

3.43.4 4.04.0 POSPOS 1:161:16

5.55.5 6.46.4 POSPOS 1:641:64

3.83.8 4.14.1 POSPOS 1:321:32

2.72.7 2.22.2 POSPOS 1:161:16

4.34.3 5.95.9 POSPOS 1:1281:128

3.93.9 6.36.3 POSPOS >1:256>1:256

0.950.95 0.470.47 NEGNEG 1:161:16

3.53.5 2.42.4 POSPOS 1:161:16

1.21.2 0.70.7 NEGNEG 1:16*1:16*

5.75.7 6.16.1 POSPOS >1:256>1:256*also Leish IFA reactive

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Leishmania TestingLeishmania Testing

All reactive, RIPA unconfirmed (IR in IND; RR in IVD) All reactive, RIPA unconfirmed (IR in IND; RR in IVD) sent to Focus for sent to Focus for LeishmaniaLeishmania IgM/IgG IFA IgM/IgG IFA– 4 species: 4 species: L. donovani, L. braziliensis, L. tropica, L. L. donovani, L. braziliensis, L. tropica, L.

mexicanamexicana IND: 65 IRs => 36 sent for IND: 65 IRs => 36 sent for LeishLeish testing (index, ret’d testing (index, ret’d

plasma unit and follow up)plasma unit and follow up)– 31 RIPA neg; 5 RIPA pos (due to low level EIA; S/CO 31 RIPA neg; 5 RIPA pos (due to low level EIA; S/CO

values of 0.93-1.22)values of 0.93-1.22) IVD: 104 RRs RIPA neg to date sent for IVD: 104 RRs RIPA neg to date sent for LeishLeish testing testing

(ret’d plasma only)(ret’d plasma only)

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Leishmania TestingLeishmania Testing 4 4 LeishLeish pos donors (2 IND + 2 IVD): pos donors (2 IND + 2 IVD):

– 17.5 yo female FT donor (CA) who was 17.5 yo female FT donor (CA) who was T. cruziT. cruzi RIPA neg/IFA 1:16 (+) RIPA neg/IFA 1:16 (+)• index 1:32 IgG (index 1:32 IgG (L. tropicaL. tropica)/plasma (-); plasma 1:16 IgG ()/plasma (-); plasma 1:16 IgG (L. L.

donovanidonovani)/index (-))/index (-)• Asian American; visited maternal relatives for 2 weeks in 1996 in urban Asian American; visited maternal relatives for 2 weeks in 1996 in urban

areas of Brazil (mother and grandmother lived in Brazil); no travel risk areas of Brazil (mother and grandmother lived in Brazil); no travel risk for for L. tropicaL. tropica; follow up testing negative; mother also tested negative ; follow up testing negative; mother also tested negative for for T. cruziT. cruzi and and LeishmaniaLeishmania

– 18 yo male RPT donor (CA)18 yo male RPT donor (CA)• plasma 1:16 IgG (plasma 1:16 IgG (L. donovaniL. donovani)/index (-); 3 total donations)/index (-); 3 total donations• No travel risk; follow up testing negativeNo travel risk; follow up testing negative

– 71 yo female RPT donor (MA); 2 total donations; 1:16 71 yo female RPT donor (MA); 2 total donations; 1:16 L. braziliensisL. braziliensis IgG; IgG; no follow upno follow up

– 64 yo female RPT (MI); 19 total donations; 1:20 64 yo female RPT (MI); 19 total donations; 1:20 L. braziliensisL. braziliensis IgM and IgM and 1:40 1:40 L. donovoniL. donovoni IgM; no follow up IgM; no follow up

Likely all false pos for both Likely all false pos for both T. cruziT. cruzi by EIA and by EIA and LeishLeish by IFA by IFA Recommendation; discontinue Recommendation; discontinue LeishLeish following BPAC discussion following BPAC discussion

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Other Testing Results/ProceduresOther Testing Results/Procedures IND study IND study

– Follow up of 36 donors; 16 of 32 confirmed posFollow up of 36 donors; 16 of 32 confirmed pos

– 1/16 PCR positive; hemoculture pending/negative1/16 PCR positive; hemoculture pending/negative

– Sample handling??Sample handling??

IVD testing; pendingIVD testing; pending

““Special Protocol” for PCR and hemocultureSpecial Protocol” for PCR and hemoculture

– Increase sensitivity by having regions initiate processesIncrease sensitivity by having regions initiate processes

• Pooling EDTA whole blood samples in guanidine/EDTA soln=>PCR Pooling EDTA whole blood samples in guanidine/EDTA soln=>PCR (lyses cells and stabilizes kinetoplasts containing mutliple copies of (lyses cells and stabilizes kinetoplasts containing mutliple copies of DNA); store at 2-8CDNA); store at 2-8C

• Pooling heparinized whole blood samples, centrifuge/removal of Pooling heparinized whole blood samples, centrifuge/removal of plasma (Ab); mix buffy coat and red cells with LIT media; store at 2-8Cplasma (Ab); mix buffy coat and red cells with LIT media; store at 2-8C

• 23 samples submitted; 1 PCR pos donor to date (22 neg)23 samples submitted; 1 PCR pos donor to date (22 neg)

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IND Lookback ResultsIND Lookback Results 32 confirmed positive donors during IND32 confirmed positive donors during IND

– 17 repeat donors (allogeneic/directed)17 repeat donors (allogeneic/directed)– 140 prior donations => 170 components140 prior donations => 170 components

Of 170 componentsOf 170 components– 6 whole blood (destroyed)6 whole blood (destroyed)– 3 platelets (2 destroyed, 3 platelets (2 destroyed, 1 transfused1 transfused))– 80 red cells (7 destroyed, 80 red cells (7 destroyed, 38 transfused38 transfused, 35 pending), 35 pending)– 81 plasma (11 destroyed, 81 plasma (11 destroyed, 4 transfused4 transfused, 65 frac, 1 pending), 65 frac, 1 pending)

Of Of 1, 38 and 4 transfused components1, 38 and 4 transfused components– 11 platelet recipient => deceased 11 days post transfusion platelet recipient => deceased 11 days post transfusion– 3838 red cell recipients => 15 living, 13 deceased, 10 unknown red cell recipients => 15 living, 13 deceased, 10 unknown

• 11 recipients tested from 8 donors (red cells transfused 7-36 days); 11 recipients tested from 8 donors (red cells transfused 7-36 days); all ELISA/RIPA neg (7 also PCR neg)all ELISA/RIPA neg (7 also PCR neg)

– 44 plasma recipients => deceased plasma recipients => deceased

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IVD Lookback ResultsIVD Lookback Results 41 confirmed positive donors since licensed test implemented41 confirmed positive donors since licensed test implemented

– 21 repeat donors (allogeneic/directed)21 repeat donors (allogeneic/directed)– 171 prior donations => 108 components (reported to date)171 prior donations => 108 components (reported to date)

Of 108 componentsOf 108 components– 17 platelets (6 destroyed, 17 platelets (6 destroyed, 6 transfused, 6 transfused, 5 unknown)5 unknown)– 49 red cells (1 destroyed, 49 red cells (1 destroyed, 9 transfused9 transfused, 39 pending), 39 pending)– 41 plasma (1 destroyed, 41 plasma (1 destroyed, 2 transfused2 transfused, 27 frac, 11 pending), 27 frac, 11 pending)– 1 cryo (1 pending)1 cryo (1 pending)

Of Of 6, 9 and 2 transfused components6, 9 and 2 transfused components– 66 platelet recipients => 5 deceased, platelet recipients => 5 deceased, 1 living => ELISA and PCR neg (RIPA 1 living => ELISA and PCR neg (RIPA

pending)pending)– 99 red cell recipients => 6 deceased, 1 unknown; red cell recipients => 6 deceased, 1 unknown; 2 living => ELISA, RIPA 2 living => ELISA, RIPA

and PCR neg (RIPA pending on one)and PCR neg (RIPA pending on one)– 22 plasma recipients => plasma recipients => 2 living => ELISA neg (RIPA and PCR pending)2 living => ELISA neg (RIPA and PCR pending)

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Lookback SummaryLookback Summary

Recipients from 10 RIPA pos donors testedRecipients from 10 RIPA pos donors tested INDIND

– 11 red cell recipients tested from 8 donors 11 red cell recipients tested from 8 donors

IVDIVD– 1 platelet recipient tested from 1 donor1 platelet recipient tested from 1 donor– 2 red cell recipients tested from same donor2 red cell recipients tested from same donor– 2 plasma recipients tested from 1 donor2 plasma recipients tested from 1 donor

Total 16 recipients test negative to dateTotal 16 recipients test negative to date

E011375A (03-13-01) 27

Lookback SignificanceLookback Significance

Lookback case summary – platelets/whole blood, Lookback case summary – platelets/whole blood, considered to be highest riskconsidered to be highest risk– 1 of 4 Leiby LA and Miami (NEJM 1999)1 of 4 Leiby LA and Miami (NEJM 1999)– 4 of 9 Kirchhoff Mexico (Transfusion 2006)4 of 9 Kirchhoff Mexico (Transfusion 2006)– 0 of 1 Stramer (IVD, unpub)0 of 1 Stramer (IVD, unpub)– 5 of 14 = 36%5 of 14 = 36%

Why not higher?Why not higher?– Donor must be parasitemic (intermittent)Donor must be parasitemic (intermittent)– Parasites must remain viable/infectious in component Parasites must remain viable/infectious in component

during processing/handlingduring processing/handling– Acute infections are most frequently recognized in Acute infections are most frequently recognized in

immunosuppressed patientsimmunosuppressed patients

E011375A (03-13-01) 28

Donor DemographicsDonor Demographics 61 RR IND ARC donors61 RR IND ARC donors

– 32 RIPA pos32 RIPA pos• 14 FT, 18 RPT14 FT, 18 RPT• 19 male, 13 female19 male, 13 female• 17-84 yo (mean 47 yo; median 50 yo)17-84 yo (mean 47 yo; median 50 yo)• 30 allo, 1 auto, 1 platelet pheresis30 allo, 1 auto, 1 platelet pheresis• Countries represented (15 donor surveys received); 11/15 endemic areas: Countries represented (15 donor surveys received); 11/15 endemic areas:

Mexico (5), US (4), El Salvador (2), Bolivia (2), Guatemala (1), Argentina (1)Mexico (5), US (4), El Salvador (2), Bolivia (2), Guatemala (1), Argentina (1) 213 RR IVD ARC donors213 RR IVD ARC donors

– 41 RIPA pos41 RIPA pos• 20 FT, 21 RPT20 FT, 21 RPT• 26 male, 15 female26 male, 15 female• 39 allo, 1 auto, 1 directed (FT male)39 allo, 1 auto, 1 directed (FT male)• Countries represented (10 donor surveys received); 9/10 endemic areas: Countries represented (10 donor surveys received); 9/10 endemic areas:

Mexico (4), El Salvador (3), Brazil (1), Bolivia (1), US (1)Mexico (4), El Salvador (3), Brazil (1), Bolivia (1), US (1)

E011375A (03-13-01) 29

Donor DemographicsDonor Demographics 52 RR IVD UBS donors52 RR IVD UBS donors

– 7 + (2) RIPA pos7 + (2) RIPA pos

• 6 FT, 3 RPT6 FT, 3 RPT

• 8 males, 1 female8 males, 1 female

• 7 allo, 1 platelet pheresis, 1 auto7 allo, 1 platelet pheresis, 1 auto

• Countries represented: Mexico (4), El Salvador (2), Guatemala (1) Venezuela (1) Countries represented: Mexico (4), El Salvador (2), Guatemala (1) Venezuela (1) (1 unknown)(1 unknown)

Total 328 RR donorsTotal 328 RR donors– 82 RIPA pos82 RIPA pos

• 40 FT, 42 RPT40 FT, 42 RPT

• 53 males, 29 females53 males, 29 females

• 76 allo, 2 platelet pheresis, 3 auto, 1 directed76 allo, 2 platelet pheresis, 3 auto, 1 directed

• Countries represented (N=33): Mexico (13), El Salvador (7), US (5), Bolivia (3), Countries represented (N=33): Mexico (13), El Salvador (7), US (5), Bolivia (3), Guatemala (2), Venezuela (1), Argentina (1) Brazil (1)Guatemala (2), Venezuela (1), Argentina (1) Brazil (1)

• 28/33 (85%) endemic areas vs 28/28 controls from nonendemic (US + 1 China)28/33 (85%) endemic areas vs 28/28 controls from nonendemic (US + 1 China)

E011375A (03-13-01) 30

GenderGender Age Age (yrs)(yrs)

Born/Lived Born/Lived Endemic Country Endemic Country

Years in Years in Endemic Endemic CountryCountry

Mother Mother Endemic Endemic CountryCountry

Rural Rural Residence Residence Endemic Endemic CountryCountry

Cardiac/GI Cardiac/GI SymptomsSymptoms

FF 5050 El SalvadorEl Salvador 3535 YY Thatched roofThatched roof Racing heartbeatRacing heartbeat

F F (runner)(runner)

6060 US onlyUS only n/an/a NN NN Racing heartbeatRacing heartbeat

MM 5050 BoliviaBolivia 66 YY NN NoneNone

MM 5757 MexicoMexico 1111 YY NN NoneNone

F (vet)F (vet) 6464 US born/lived in US born/lived in MexicoMexico

n/an/a NN NN Irreg heartbeatIrreg heartbeat

MM 7676 MexicoMexico 2929 YY NN Swollen anklesSwollen ankles

F (LB)F (LB) 3434 El SalvadorEl Salvador 2929 YY Thatched roof; Thatched roof; mud floors, bittenmud floors, bitten

Visible neck veinsVisible neck veins

MM 3939 BoliviaBolivia 1111 Y (w/cardiac Y (w/cardiac symptoms)symptoms)

Thatched roof; Thatched roof; mud floors, bittenmud floors, bitten

None, but yes for None, but yes for maternal familymaternal family

FF 6666 GuatemalaGuatemala 2727 YY Thatched roof; Thatched roof; mud floorsmud floors

Extra heart Extra heart soundssounds

FF 5757 US onlyUS only n/an/a NN NN NoneNone

F (PCR+)F (PCR+) 2929 MexicoMexico 1515 YY Thatched roof; Thatched roof; mud floorsmud floors

NoneNone

MM 5959 MexicoMexico 1919 YY Thatched roof; Thatched roof; mud floors, bittenmud floors, bitten

ECG irreg, diff. ECG irreg, diff. breathingbreathing

MM 4242 MexicoMexico 2121 YY Mud floorsMud floors Sticking sens Sticking sens esophagus, stomachesophagus, stomach

E011375A (03-13-01) 31

GenderGender Age Age (yrs)(yrs)

Born/Lived Born/Lived Endemic Endemic Country Country

Years in Years in Endemic Endemic CountryCountry

Mother Mother Endemic Endemic CountryCountry

Rural Residence Rural Residence Endemic CountryEndemic Country

Cardiac/GI Cardiac/GI SymptomsSymptoms

MM 5757 ArgentinaArgentina 1212 YY NN Racing heartbeatRacing heartbeat

F (preg; F (preg; f/u CDC)f/u CDC)

3333 El SalvadorEl Salvador 1818 YY NN ECG irreg; multiple ECG irreg; multiple otherother

MM 7575 MexicoMexico 2020 YY Dirt floorDirt floor Shortness breathShortness breath

F F (6 (6 children children

tested neg)tested neg)

5656 MexicoMexico 1919 YY Dirt floorDirt floor Shortness breathShortness breath

M M (PCR+)(PCR+)

2727 El SalvadorEl Salvador 1818 YY NN ECG irreg; multiple ECG irreg; multiple otherother

FF 4242 MexicoMexico 3333 Y (w/cardiac Y (w/cardiac symptoms)symptoms)

YY Shortness of breathShortness of breath

FF 5757 BrazilBrazil 4646 YY Thatched roof; Thatched roof; mud floorsmud floors

Shortness of breathShortness of breath

MM 5757 El SalvadorEl Salvador 3333 YY Thatched roof; Thatched roof; mud floorsmud floors

ECG irreg; multiple ECG irreg; multiple otherother

F F 3333 BoliviaBolivia 33 Y (w/cardiac Y (w/cardiac symptoms)symptoms)

NN Shortness of breathShortness of breath

MM 5050 US onlyUS only n/an/a NN n/an/a Trouble swallowingTrouble swallowing

MM 2828 MexicoMexico 1717 YY Dirt floorDirt floor Racing heartbeatRacing heartbeat

E011375A (03-13-01) 32

Possible Autochthonous CasesPossible Autochthonous Cases 61 yo female (CA) runner in Griffith Park61 yo female (CA) runner in Griffith Park

– Griffith park zoo and other animals demonstrated to harbor Griffith park zoo and other animals demonstrated to harbor T. cruziT. cruzi (6 sp of triatomine bugs in (6 sp of triatomine bugs in CA; 18 mammal species are reservoirs)CA; 18 mammal species are reservoirs)

– Lived in LA entire life, high quality housingLived in LA entire life, high quality housing– Travel outside of the USTravel outside of the US

• Time share in Cancun where she spends a week 1990-1999; no campingTime share in Cancun where she spends a week 1990-1999; no camping 64 yo female (AZ) retired vet64 yo female (AZ) retired vet

– Lived in rural Mexico where she volunteered as a vet/exposure to infectious materialLived in rural Mexico where she volunteered as a vet/exposure to infectious material 57 yo female (CA) lives in rural area57 yo female (CA) lives in rural area

– Rural area recovering from fire damageRural area recovering from fire damage– Has many pets and frequently sees raccoons, opossums, skunks on her property and adjacent Has many pets and frequently sees raccoons, opossums, skunks on her property and adjacent

property, also gardens on her propertyproperty, also gardens on her property– Lived in LA entire life, high quality housingLived in LA entire life, high quality housing– Multiple transfusions in 1971 in CAMultiple transfusions in 1971 in CA– AsymptomaticAsymptomatic

50 yo male (AR)50 yo male (AR)– Lived in US entire life; one trip to NassauLived in US entire life; one trip to Nassau– AsymptomaticAsymptomatic– Only possible “risk” is time spend in Corpus Christi, TX where he slept outside for several Only possible “risk” is time spend in Corpus Christi, TX where he slept outside for several

weeksweeks

E011375A (03-13-01) 33

Summary and ConclusionsSummary and Conclusions Prevalence 1:21,100Prevalence 1:21,100

– 82 RIPA pos donors from 328 RR donors in 17 states during 82 RIPA pos donors from 328 RR donors in 17 states during IND/IVD testing of >1.9 million donationsIND/IVD testing of >1.9 million donations

– 60% from California and Florida 60% from California and Florida LeishmaniaLeishmania

– Adds no value; only confusion!Adds no value; only confusion! Lookback (to date)Lookback (to date)

– 60 transfused components from 278 mfg’d from 38 RIPA pos donors60 transfused components from 278 mfg’d from 38 RIPA pos donors– 16 recipients tested neg from 10 donors; 16 recipients tested neg from 10 donors; only 1 platelet recipientonly 1 platelet recipient

Donor DemographicsDonor Demographics– 28/33 (85%) endemic areas vs 28/28 controls from nonendemic (US 28/33 (85%) endemic areas vs 28/28 controls from nonendemic (US

+ 1 China)+ 1 China)– 5 possible autochthonous cases; time of infection unknown5 possible autochthonous cases; time of infection unknown

E011375A (03-13-01) 34

AcknowledgementsAcknowledgements

American Red CrossAmerican Red Cross– Greg Foster, SSOGreg Foster, SSO

– David Leiby, HLDavid Leiby, HL

– Roger Dodd, HLRoger Dodd, HL

– Ross Herron, West DivRoss Herron, West Div

– Pamela Kahm, West DivPamela Kahm, West Div

– Norma Espinoza, West DivNorma Espinoza, West Div

– Kay Crull, West DivKay Crull, West Div

– Muriel Nelson, ITMuriel Nelson, IT

– Mike Savin, ITMike Savin, IT

Blood Systems LaboratoriesBlood Systems Laboratories– Sally CagliotiSally Caglioti

– Frank RadarFrank Radar

– Larry MorganLarry Morgan

Ortho Clinical DiagnosticsOrtho Clinical Diagnostics– Cheryl VitowCheryl Vitow

– Cindy BallasCindy Ballas

– Brian McDonoughBrian McDonough