Guidance for Industry: Use of Serological Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Whole Blood and Blood Components Intended for Transfusion

Guidance for Industry
Use of Serological Tests to Reduce the
Risk of Transmission of Trypanosoma
cruzi Infection in Whole Blood and
Blood Components Intended for
Transfusion

Additional copies of this guidance are available from the Office of Communication, Outreach
and Development (OCOD) (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 208521448, or by calling 1-800-835-4709 or 301-827-1800, or email [email protected], or from the
Internet at
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm.
For questions on the content of this guidance, contact OCOD at the phone numbers listed above.

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
December 2010
OMB Control No. 0910-xxxx
Expiration Date: xx/xx/xxxx
See additional PRA statement in Section VI of this guidance

Contains Nonbinding Recommendations

TABLE OF CONTENTS
I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2
A.
B.

III.

Blood Donor Screening Tests for Chagas Disease in the United States ........... 2
Risk of T. cruzi Infection from Transfusion of Whole Blood and Blood
Components ........................................................................................................... 4

RECOMMENDATIONS.................................................................................................. 5
A.
B.
C.

Blood Donor Testing and Management .............................................................. 5
Product Management ........................................................................................... 6
Reporting Changes to an Approved Application............................................... 9

IV.

IMPLEMENTATION .................................................................................................... 10

V.

REFERENCES................................................................................................................ 11

VI.

PAPERWORK REDUCTION ACT OF 1995.............................................................. 14

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Contains Nonbinding Recommendations

Guidance for Industry
Use of Serological Tests to Reduce the Risk of Transmission of
Trypanosoma cruzi Infection in Whole Blood and Blood Components
Intended for Transfusion
This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this
topic. It does not create or confer any rights for or on any person and does not operate to bind
FDA or the public. You can use an alternative approach if the approach satisfies the
requirements of the applicable statutes and regulations. If you want to discuss an alternative
approach, contact the appropriate FDA staff. If you cannot identify the appropriate FDA staff,
call the appropriate number listed on the title page of this guidance.

I.

INTRODUCTION

We, FDA, are issuing this guidance to notify you, establishments that manufacture Whole Blood
and blood components intended for transfusion, about FDA approvals of Biologics License
Applications (BLAs) for serological test systems for the detection of antibodies to Trypanosoma
cruzi (T. cruzi). These tests are intended for use as donor screening tests to reduce the risk of
transmission of T. cruzi infection by detecting antibodies to T. cruzi in plasma and serum
samples from individual human donors. This guidance does not apply to establishments that
make eligibility determinations for donors of human cells, tissues, and cellular and tissue-based
products (HCT/Ps). Also, this guidance document does not apply to the collection of Source
Plasma.
In addition, we are providing you with recommendations for testing donations of Whole Blood
and blood components for evidence of T. cruzi infection, blood donor and product management,
labeling of Whole Blood and blood components, and procedures for reporting the
implementation of a licensed T. cruzi test at your facility or at your contract testing laboratory, as
required for licensed manufacturers of blood and blood components under Title 21 Code of
Federal Regulations 601.12 (21 CFR 601.12).
This guidance finalizes the draft guidance entitled, “Guidance for Industry: Use of Serological
Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Whole Blood and
Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue-Based
Products (HCT/Ps)” dated March 2009.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe FDA’s current thinking on a topic and should be
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.
The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.

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Contains Nonbinding Recommendations

II.

BACKGROUND

Chagas disease is caused by the protozoan parasite, T. cruzi. The disease is considered endemic
in Mexico and Central and South America; rarely, the pathogenic agent has been reported to
cause human infection in the United States (U.S.) by natural vector transmission (Ref. 1).
Natural infections are transmitted mainly when the feces of certain blood sucking insects
(triatomine bugs, commonly referred to as kissing or chinch bugs) that harbor the infection are
rubbed into a bug bite, other wound, or directly into the eyes or mucous membranes. Other
primary forms of transmission include congenital (mother to unborn infant), organ
transplantation, and blood transfusion. Current estimates are that at least 11 million persons in
Mexico and Central and South America carry the parasite chronically and could present a
potential source of infection should they become donors. The presence of the pathogenic agent
in U.S. and Canadian donors is increasing due to immigration of infected individuals from
endemic areas. Experts estimate that there may be as many as 300,000 persons unknowingly
infected with T. cruzi, who reside in the U.S. and Canada (Ref. 2).
Vector-borne T. cruzi infections are mostly mild in the acute phase and then persist throughout
life, usually without symptoms. Acute infection in patients with compromised immune systems,
for example, from cancer therapy or organ transplantation, can be very serious and sometimes
fatal. Treatment options are limited, but are most effective early in the infection. The lifetime
risk of severe cardiac complications (cardiomegaly, heart failure and arrhythmias) or intestinal
disorders (megacolon, megaesophagus) in infected individuals averages about 30% (range of 10
to 40% depending on a variety of factors) and may occur decades after the initial infection.
Chronic complications of Chagas disease result from the destruction of autonomic ganglia and
from myositis (Ref. 3). During the acute phase of vector-borne Chagas disease, parasites are
found in skin lesions at the site of transmission. The parasites are then spread through the
bloodstream to various tissues, particularly skeletal muscle (Ref. 4). During the chronic stage of
Chagas disease, most persons who harbor the parasite are asymptomatic and unaware of their
infection. During this phase, parasites have been demonstrated in muscle (especially cardiac
muscle), nerves, and digestive tract, but there has been very little investigation of tissue
distribution or mobilization into the circulating blood during the chronic phase (Refs. 4 through
11).
A.

Blood Donor Screening Tests for Chagas Disease in the United States

At the September 1989 Blood Products Advisory Committee (BPAC or committee)
meeting, the committee recommended testing donors of Whole Blood and blood
components for Chagas disease when a suitable test became available. In a 1995 BPAC
meeting, the committee considered whether the performance characteristics of the two
FDA-approved tests then available for diagnosis of Chagas disease would be suitable for
blood donor screening. The committee concluded that the tests discussed were not
suitable for blood donor screening. Furthermore, the committee sought clarification of
the criteria that FDA would use to license a Chagas test for donor screening. At the

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September 2002 BPAC meeting, FDA presented its then-current considerations on the
regulatory pathway and standards for licensing a donor screening test for Chagas disease
and encouraged manufacturers to develop tests based on those considerations (Ref. 12).
In December 2006, FDA issued a license to one manufacturer of an enzyme-linked
immunosorbent assay (ELISA) test system for the detection of antibodies to T. cruzi in
donors.1 Since the end of January 2007, a number of blood centers representing a large
proportion of U.S. blood collections have been testing donors using this licensed assay.
Blood donor testing by a serological test system identifies donors that are repeatedly
reactive for antibodies to T. cruzi. The presence of antibodies to T. cruzi is strong
evidence that a donor is infected with this parasite. Most donors that are repeatedly
reactive by a serological test system and confirmed by additional medical diagnostic
testing for antibodies to T. cruzi have chronic, asymptomatic infections acquired years
earlier during residence in areas endemic for T. cruzi. Therefore, prior donations from a
donor who is repeatedly reactive on an ELISA test system may have harbored T. cruzi
parasites.
At the April 2007 BPAC meeting, the committee was asked to comment on scientific
issues that FDA should consider in developing its recommendations on implementation
of blood donor screening for antibodies to T. cruzi (Ref. 13). Issues discussed by the
committee included the public health significance of Chagas disease, the need for
additional data on the prevalence, incidence and risk of transmission of T. cruzi infection
by transfusion, the performance characteristics of the antibody test, including the need for
additional data on the correlation of test results with parasitemia, and the lack of a
licensed supplemental test for confirmatory testing.
The committee also commented on the design of research studies to validate a strategy
for selective testing of repeat blood donors. It noted that a period of universal testing of
all blood donors would generate critical data on the prevalence of T. cruzi infections in
U.S. blood donors and that donor questions for selective donor screening needed
validation.
At the April 2009 BPAC meeting, FDA sought advice from the committee regarding
selective testing strategies for T. cruzi infection in repeat blood donors. At the meeting,
the agency presented several potential testing strategies for T. cruzi infection in
individual blood donors and a risk analysis for selective testing strategies (Ref. 14).
Issues discussed at the meeting included the epidemiology of Chagas disease in the U.S.,
the experience with blood donor testing for T. cruzi antibodies during the timeframe of
January 2007 through November 2008 (i.e., since the first test was approved and
implemented), and the experience with asking donors questions to assess their risk of
having acquired Chagas disease. After discussing the testing strategies presented, the
committee voted in favor of a selective testing strategy in which one negative test would
qualify a donor for all future donations without further testing or the need to be asked
1

ORTHO T. cruzi ELISA Test System, Ortho-Clinical Diagnostics, Inc., Raritan, NJ.

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questions regarding risk of a newly acquired infection (Ref. 14). The committee’s
recommendation was contingent upon the continuation of studies to define the incidence
of new infections in previously screened negative donors.
A second serological test for detection of antibodies to T. cruzi in donors was licensed on
April 30, 2010.2
B.

Risk of T. cruzi Infection from Transfusion of Whole Blood and Blood
Components

Blood donations from individuals from endemic areas are the primary source of risk for
T. cruzi infection from transfusion. Studies in the mid-1990s (Ref. 15) estimated that the
rate of seropositive blood donors in the U.S. ranged from 1 in 5,400 to 1 in 25,000,
largely depending on the proportion of immigrants from Chagas endemic areas present in
the population where the studies were conducted. However, more recent studies in the
areas where donor testing has been performed over a period of time suggest that these
rates have increased. For example, a rate of 1 in 2,000 was found recently in the Los
Angeles metropolitan area (Ref. 16) compared with a previous rate of 1 in 7,500 (Ref.
15). Transfusion transmission in endemic areas has been a major public health concern,
and many countries considered endemic for T. cruzi infection screen blood donors for the
presence of antibody.
In the U.S. and Canada, only seven cases of transfusion-transmitted T. cruzi infections
(Refs. 17 through 21) and five cases of infection from organ transplantation (Refs. 22 and
23) have been documented. Since the initiation of blood donor screening, two cases of
transmission involving platelet products were discovered through a lookback study of a
confirmed T. cruzi positive donor (Ref. 24). However, transfusion or transplantassociated transmission of T. cruzi infection in immunocompetent patients is not likely to
be diagnosed, and in many cases, even if symptoms appear, infection may not be
recognized (Ref. 25).
Studies in blood centers that ask donors questions about birth and/or residence in a
T. cruzi-endemic country have shown such questions not to be completely effective at
identifying seropositive donors. Studies also have looked at the rate of transfusion
transmitted infection from T. cruzi antibody-positive individuals. Published lookback
studies in the U.S. and in Mexico of 22 transfusion recipients of seropositive donations,
identified five of these recipients (22.7%) who later tested positive for antibodies
suggesting transfusion transmission of T. cruzi (Refs. 20, 26 and 27). This transmission
rate of 22.7% is consistent with the literature from Latin America on rates of blood-borne
transmission from seropositive donors in Mexico and Central and South America (Ref.
28). However, lookback studies conducted using the licensed ELISA test reported at the
April 2009 BPAC meeting (Ref. 14) described 242 cases of transfusions of prior
collections from seropositive donors that resulted in two T. cruzi confirmed positive
transmissions (0.83%). These results indicate that the risk of T. cruzi infection
transmission by transfusion of a seropositive unit in the U.S. may be much lower than
2

ABBOTT PRISM Chagas, Abbott Diagnostics, Abbott Park, IL.

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Contains Nonbinding Recommendations
previously thought. We note that these studies have confirmed the demographic
characteristics of the typical seropositive donor as an immigrant from a T. cruzi-endemic
country with an asymptomatic, chronic infection. However, the data also suggest that
there are seropositive individuals who acquired their infections within the U.S. (Ref. 29).
Despite these new data, the rate of transfusion transmission of T. cruzi infection in the
U.S. continues to be uncertain because of the limited number of studies conducted to
date. In particular, the incidence of T. cruzi infections and the rate of transfusion
transmission in the U.S. remain under investigation.

III.

RECOMMENDATIONS
A.

Blood Donor Testing and Management
1. Identify Donors with a History of Chagas Disease
We recommend that you ask the following question to all donors at each donation,
to identify donors with a history of Chagas disease:
“Have you ever had Chagas disease?” 3
You should indefinitely defer donors who answer “yes” to this question.
2. Donor Testing
We recommend one time testing of each donor of allogeneic units of blood using
a licensed test for antibodies to T. cruzi.4 Donors who test nonreactive are
qualified to return to donate without further testing of subsequent donations for
antibodies to T. cruzi. Each blood establishment should review its records5 to
determine the history of testing for T. cruzi in prospective donors to determine
whether a donor should be tested.
We also recommend one time testing of autologous blood donors using a licensed
test for antibodies to T. cruzi when the circumstances described in
21 CFR 610.40(d)(1) through (3) are applicable.

3

FDA recognizes the Full-Length Donor History Questionnaire (DHQ) Documents, Version 1.3, dated May 2008,
and DHQ Version 1.1, dated June 2005, as an acceptable mechanism for collecting donor history information
because it is consistent with FDA requirements and recommendations.
4
FDA intends to reevaluate the recommendation for one time testing after reviewing the outcome of ongoing studies
of the risk of newly acquired cases of T. cruzi infection together with other relevant information.
5
Blood establishments are required to maintain donor and processing records under 21 CFR 606.160.

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3. Donor Deferral
We recommend that all donors who test repeatedly reactive on a licensed test for
T. cruzi antibody or who have a history of Chagas disease should be indefinitely
deferred and notified of their deferral.
4. Donor Counseling
We recommend that donors who test repeatedly reactive using a licensed test for
antibodies to T. cruzi be informed about the likelihood and medical significance
of infection with T. cruzi within 8 weeks after determining that the donor is not
suitable for donation. Additional medical diagnostic testing may provide
information useful in donor counseling.
All donors who test repeatedly reactive should be counseled to seek a physician’s
advice. It also may be useful to refer them to their state and local health
departments or to other appropriate community resources.
Because the licensed tests have demonstrated some reactivity in donors infected
with pathogens other than T. cruzi, e.g., Leishmania, notification of the donor
should include an explanation of the significance of this cross-reactivity.
5. Donor Reentry Criteria
At this time, there is no FDA licensed supplemental test for antibodies to T. cruzi
that can be used for confirmation of true positive screening test results. When
such a test becomes available, a positive test result will provide further
confirmation of true positive screening test results. Given the lack of such a
supplemental test, FDA is not currently recommending reentry criteria for blood
donors deferred on the basis of a repeatedly reactive screening test for antibodies
to T. cruzi.
B.

Product Management
1. Index Donations
We recommend that blood and blood components from repeatedly reactive index
donations be quarantined and destroyed.6 Blood and blood components
determined to be unsuitable for transfusion and which are not destroyed (e.g.,
used for research) must be prominently labeled: “NOT FOR TRANSFUSION,”
and the label must state the reason the unit is considered unsuitable (e.g., the
component is positive for T. cruzi (21 CFR 606.121(f)).

6

Though the risk of transmission by transfusion varies by component, highest in Whole Blood and Platelets and
lowest in plasma, quarantine and destruction are recommended for all blood and blood components from repeatedly
reactive index donations as a prudent safeguard against transmission.

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Contains Nonbinding Recommendations
2. Lookback (Product Retrieval and Consignee Notification)
Within 3 calendar days after a donor tests repeatedly reactive by a licensed test for
T. cruzi antibody, you should:
•

•
•

identify all in-date blood and blood components previously donated by
such a donor, going back either 10 years (or indefinitely where electronic
records are available), or else, in a previously tested donor, 12 months
prior to the donor’s most recent negative test result with a licensed test for
T. cruzi antibody, whichever is the lesser period (the lookback period),
though it is recognized that under the selective testing recommended
herein, most donors tested will not have a prior negative test.
quarantine all previously collected in-date blood and blood components
held at your establishment; and
notify consignees of all previously collected in-date blood and blood
components to quarantine and return the blood and blood components to
you or to destroy them.

In addition, when you identify a donor who is repeatedly reactive by a licensed
test for T. cruzi antibodies and for whom there is additional information indicating
risk of T. cruzi infection, such as testing positive on a licensed supplemental test
(when such test is available), or until such test is available, information that the
donor or the donor’s mother resided in an area endemic for Chagas disease
(Mexico, Central and South America), or as a result of other medical diagnostic
testing of the donor indicating T. cruzi infection, we recommend that you:
• notify consignees of all previously distributed blood and blood
components collected during the lookback period; and
• if blood or blood components were transfused, encourage consignees to
notify the recipient’s physician of record of a possible increased risk of
T. cruzi infection.
We recommend that when there is additional information indicating risk of
T. cruzi infection, you make such notifications within 12 weeks of obtaining the
repeatedly reactive test result.
Retrospective Review of Records
If you are a blood establishment that implemented screening with a licensed test
for antibodies to T. cruzi prior to the effective date of this guidance, you may wish
to perform a retrospective review of records to identify donors:
•
•

with repeatedly reactive test results by a licensed test for T. cruzi
antibodies; and
for whom there is additional information indicating risk of T. cruzi
infection, such as geographical risk for exposure in an endemic area, or
medical diagnostic testing of the donor.

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Note: There currently is no licensed T. cruzi supplemental test. When such a test
is available, a positive test result will provide additional information indicating
risk of T. cruzi infection.
If a donor is identified as being at risk of infection of T. cruzi during the
retrospective review, you should consider performing all the lookback actions
described above.
3. Autologous Donations
Although autologous use of blood does not increase a patient’s/donor’s risk of
illness from a pre-existing infection, FDA regulations under 21 CFR 610.40(d)
and (e) require testing of autologous blood donors under certain circumstances to
prevent inadvertent allogeneic exposures to unsuitable units.
a. We recommend that blood and blood components from autologous donors
that are repeatedly reactive by a licensed test for T. cruzi antibody be
released for autologous use only with approval of the autologous donor’s
referring physician. Establishments should provide the results of any
additional testing for antibodies to T. cruzi, as available, to the autologous
donor’s referring physician.
b. Each autologous donation must be labeled as required under
21 CFR 610.40(d)(4) and 606.121(i)(4), as appropriate. Given the
seriousness of T. cruzi infections, autologous donations that are repeatedly
reactive by a licensed test for T. cruzi antibody should bear a
“BIOHAZARD” legend. See 21 CFR 610.40(d)(4).
4. Circular of Information
Consistent with the implementation of other donor screening tests, licensed and
unlicensed establishments must update the instruction circular, also known as the
“Circular of Information” to state that a licensed test for antibodies to T. cruzi was
used to screen donors and that the results of testing were negative
(21 CFR 606.122(h)). We recommend the following statement:
“All blood has been collected from donors who have tested negative
by a licensed test for antibodies to T. cruzi either on the current
donation or at least one previous donation.”

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5. Biological Product Deviation Report and Fatality Report
Under 21 CFR 606.171, licensed manufacturers, unlicensed registered blood
establishments, and transfusion services must report any event and information
associated with the manufacturing, if the event either represents a deviation from
current good manufacturing practice, applicable regulations, applicable standards,
or established specifications that may affect the safety, purity, or potency of the
product; or represents an unexpected or unforeseeable event that may affect the
safety, purity, or potency of the product, and it occurs in your facility or another
facility under contract with you and involves distributed blood or blood
components. For additional information regarding reporting, you may refer to the
FDA guidance, “Guidance for Industry: Biological Product Deviation Reporting
for Blood and Plasma Establishments,” dated October 2006 (Ref. 30). Also, when
a complication of blood collection or transfusion (e.g., involving T. cruzi) is
confirmed to be fatal, you must notify FDA in accordance with
21 CFR 606.170(b).
C.

Reporting Changes to an Approved Application

Licensed blood establishments must report the changes to an approved application to
FDA in the following manner. Unlicensed blood establishments do not need to report the
changes to FDA.
1. Revision of Donor History Questionnaire
a. Licensed establishments that have already reported implementation of the
use of the DHQ documents found acceptable by FDA cited herein or the
use of a questionnaire that includes the recommended question on Chagas
disease do not need to report implementation of the question to FDA
again.
b. If you are a licensed establishment and you revise your donor history
questionnaire to include the recommended question on Chagas disease,
you must report the revision as a minor change in your Annual Report
(AR) in accordance with 21 CFR 601.12(d), noting the date the change
was implemented.
2. Test Implementation
a. If you are a licensed blood establishment and you begin using a licensed
serological test for the detection of antibodies to T. cruzi according to the
manufacturer’s product insert in your facility, then you must notify us of
the testing change in your AR, in accordance with 21 CFR 601.12(d). If
you already have an approved supplement to your BLA to use a contract
laboratory to perform infectious disease testing of blood products, and the

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Contains Nonbinding Recommendations
contract laboratory will now perform a serological test for antibodies to
T. cruzi, you must report this change in your AR, in accordance with
21 CFR 601.12(d).
b. If you are a licensed blood establishment and you use a new contract
laboratory to perform a serological test for antibodies to T. cruzi (provided
the laboratory is registered with FDA and has been performing donor
testing), you must report this change to FDA by submission of a
“Supplement - Changes Being Effected” in accordance with
21 CFR 601.12(c)(1) and (5). Note that if your contract laboratory has not
previously performed infectious disease testing for blood products, then
you must report this change as a major change in a prior approval
supplement in accordance with 21 CFR 601.12(b).
3. Circular of Information
a. If you are a licensed blood establishment and you revise your Circular of
Information, you must submit the revised labeling in a “Special Labeling
Supplement – Changes Being Effected” in accordance with
21 CFR 601.12(f)(2), provided that the revision is identical to the
recommended statement.
b. If you are a licensed blood establishment and you wish to use a different
statement, then you must submit the labeling change in accordance with
21 CFR 601.12(f)(1).

IV.

IMPLEMENTATION

We recommend that you implement the recommendations contained in this guidance within 12
months of the issuance of the guidance.

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V.

REFERENCES
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Wesson (2007). “Autochthonous transmission of Trypanosoma cruzi, Louisiana.” Emerg
Infect Dis 13(4): 605-607.
2. Bern, C. and Montgomery, S., (2009). “An estimate of the burden of Chagas disease in
the United States.” CID 49: e52-54.
3. Infectious Diseases: The Clinician’s Guide to Diagnosis, Treatment and Prevention.
David C. Dale, MD ed., WebMD, Inc., New York, NY.
4. World Health Organization. Control of Chagas Disease. WHO Expert Committee on the
Control of Chagas Disease (2000: Brasilia, Brazil), Control of Chagas Disease: Second
report of the WHO Expert committee, 2002.
5. Bellotti, G., E. A. Bocchi, A. V. de Moraes, M. L. Higuchi, M. Barbero-Marcial, E. Sosa,
A. Esteves-Filho, R. Kalil, R. Weiss, A. Jatene and F. Pileggi (1996). “In vivo detection
of Trypanosoma cruzi antigens in hearts of patients with chronic Chagas’ heart disease.”
Am Heart J 131(2): 301-307.
6. Vago, A. R., A. M. Macedo, S. J. Adad, D. D. Reis and R. Correa-Oliveira (1996). “PCR
detection of Trypanosoma cruzi DNA in oesophageal tissues of patients with chronic
digestive Chagas’ disease.” Lancet 348: 891-892.
7. Añez, N., H. Carrasco, H. Parada, G. Crisante, A. Rojas, C. Fuenmayor, N. Gonzalez, G.
Percoco, R. Borges, P. Guevara and J. L. Ramirez (1999). “Myocardial parasite
persistence in chronic chagasic patients.” Am J Trop Med Hyg 60(5): 726-732.
8. Jones, E.M., D. G. Colley, S. Tostes, E. R. Lopes, C. L. Vnencak-Jones, and T. L.
McCurley (1993). “Amplification of a Trypanosoma cruzi DNA sequence from
inflammatory lesions in human chagasic cardiomyopathy.” Am J Trop Med Hyg 48(3):
348-357.
9. Vago, A. R., L. O. Andrade, A. A. Leite, D. d’Avila Reis, A. M. Macedo, S. J. Adad, S.
Tostes Jr., M.C. V. Moreira, G. B. Filho, S. D. J. Pena (2000). “Genetic characterization
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10. Virreira, M., G. Serrano, L. Maldonado, and M. Svoboda (2006). “Trypanosoma cruzi:
Typing of genotype (sub)lineages in megacolon samples from bolivian patients.” Acta
Tropica 100(3): 252-255.

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11. da Silva Manoel-Caetano, F., C.M. Carareto, A. A. Borim, K. Miyazaki, and A.E. Silva
(2008). “kDNA gene signatures of Trypanosoma cruzi in blood and oesophageal mucosa
from chronic chagasic patients.” Trans R Soc Trop Med Hyg 102(11): 1102-1107.
12. Blood Products Advisory Committee, 74th Meeting, September 12, 2002
http://www.fda.gov/ohrms/dockets/ac/02/transcripts/3892t1-01.pdf accessed November
17, 2010.
13. Blood Products Advisory Committee, 89th Meeting, April 26-27, 2007
http://www.fda.gov/ohrms/dockets/ac/07/minutes/2007-4300M.pdf accessed November
17, 2010.
14. Blood Products Advisory Committee, 94th Meeting, April 1, 2009
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Bloo
dVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/UCM155628.pdf
accessed November 17, 2010.
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“Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor
demographics on seroprevalence and implications for transfusion transmission.”
Transfusion 42(5): 549-555.
16. Strong, D. M. and K. Shoos-Lipton (2006). “Information Concerning Implementation of
a Licensed Test for Antibodies to Trypanosoma cruzi.” AABB Bulletin #06-08.
17. Saulnier Sholler, G. L., S. Kalkunte, C. Greenlaw, K. McCarten and E. Forman (2006).
“Antitumor activity of nifurtimox observed in a patient with neuroblastoma.” J Pediatr
Hematol Oncol 28(10): 693-695.
18. Young, C., P. Losikoff, A. Chawla, L. Glasser and E. Forman (2007). “Transfusionacquired Trypanosoma cruzi infection.” Transfusion 47(3): 540-544.
19. Cimo, P. L., W. E. Luper and M. A. Scouros (1993). “Transfusion-associated Chagas’
disease in Texas: report of a case.” Tex Med 89(12): 48-50.
20. Leiby, D. A., B. A. Lenes, M. A. Tibbals and M. T. Tames-Olmedo (1999). “Prospective
evaluation of a patient with Trypanosoma cruzi infection transmitted by transfusion.” N
Engl J Med 341(16): 1237-1239.
21. Lane, D. J., G. Sher, B. Ward, M. Ndao, D. Leiby, B. Hewlett and E. Bow (2000).
“Investigation of the second case of transfusion transmitted Chagas disease in Canada.”
42nd Annual Meeting of the American Society of Hematology, San Francisco, CA.
22. CDC. C.F. Zayas, C. Perlino, A. Caliendo, D. Jackson, E. J. Martinez, P. Tso, T. G.
Heffron, J. L. Logan, B. L. Herwaldt, et.al. (2002). “Chagas disease after organ
transplantation--United States, 2001.” MMWR Morb Mortal Wkly Rep 51(10): 210-212.

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23. CDC. L. Mascola, B. Kubak, S. Radhakrishna, T. Mone, R. Hunter, D. A. Leiby, M.
Kuehnert, A. Moore, F. Steurer, G. Lawrence and H. Kun (2006). “Chagas disease after
organ transplantation--Los Angeles, California, 2006.” MMWR Morb Mortal Wkly Rep
55(29): 798-800.
24. Kessler, D., K. M. Grima, C. D. Hillyer (2010) “Chagas transmission identified through
lookback” Transfusion 50 (2S): 31A-32A.
25. Leiby, D. A., F. J. Rentas, K. E. Nelson, V. A. Stambolis, P. M. Ness, C. Parnis, H. A.
McAllister, Jr., D. H. Yawn, R. J. Stumpf and L. V. Kirchhoff (2000). “Evidence of
Trypanosoma cruzi infection (Chagas’ disease) among patients undergoing cardiac
surgery.” Circulation 102(24): 2978-2982.
26. Leiby, D. A., E. J. Read, B. A. Lenes, A. J. Yund, R. J. Stumpf, L. V. Kirchhoff and R.
Y. Dodd (1997). “Seroepidemiology of Trypanosoma cruzi, etiologic agent of Chagas’
disease, in US blood donors.” J Infect Dis 176(4): 1047-1052.
27. Kirchhoff, L. V., P. Paredes, A. Lomelí-Guerrero, M. Paredes-Espinoza, C. S. RonGuerrero, M. Delgado-Mejia and J. G. Peña-Muñoz (2006). “Transfusion-associated
Chagas disease (American trypanosomiasis) in Mexico: implications for transfusion
medicine in the United States.” Transfusion 46(2): 298-304.
28. Schmunis, G. A. (1999). “Prevention of transfusional Trypanosoma cruzi infection in
Latin America.” Mem Inst Oswaldo Cruz 94 (Suppl 1): 93-101.
29. Bern, C., S. P. Montgomery, L. Katz, S. Caglioti and S. L. Stramer (2008). “Chagas
disease and the US blood supply.” Curr Op Infect Dis 21:476–482.
30. FDA “Guidance for Industry: Biological Product Deviation Reporting for Blood and
Plasma Establishments,” October 2006,
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformatio
n/Guidances/Blood/ucm073455.htm accessed November 17, 2010.

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Contains Nonbinding Recommendations
VI.

PAPERWORK REDUCTION ACT OF 1995

This guidance contains information collection provisions that are subject to review by the Office of
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 35013520).
We believe that the information collection provisions in the guidance do not create a new burden for
establishments. We believe the provisions recommended in this guidance are part of usual and
customary business practices. The information collection provisions contained in the guidance are for
establishments that manufacture Whole Blood and blood components intended for transfusion to
notify consignees and such consignees to notify the recipient’s physician of record. Since the end
of January 2007, a number of blood centers representing a large proportion of U.S. blood
collections have been testing donors using a licensed assay. We believe these establishments
have already developed standard operating procedures when a donor is repeatedly reactive by a
licensed test for T. cruzi antibodies and for whom there is additional information indicating risk
of T. cruzi infection for notifying consignees and to encourage the consignees to notify the blood
and blood components recipient’s physician of record. Licensed manufacturers are required to
notify FDA of the implementation of the licensed T. cruzi test at your facility or contract testing
laboratory.

This guidance also refers to previously approved collections of information found in FDA
regulations. The collections of information in 21 CFR 601.12 have been approved under OMB
control no. 0910-0338; the collections of information in 21 CFR 606.100, 606.121, 606.122,
606.160(b)(ix), 606.170(b), 610.40, and 630.6 have been approved under OMB control no. 09100116; the collections of information in 21 CFR 606.171 have been approved under OMB control
no. 0910-0458.
An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB control number. The OMB control number
for this information collection is 0910-xxxx (Expires xx/xx/xxxx). NOTE: FDA will publish a
notice concerning OMB approval of these requirements in the FEDERAL REGISTER prior to
the implementation date of this guidance and will update this information accordingly.

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