Use of Serological Tests to 
Reduce the Risk of 
Transmission of Trypanosoma 
cruzi Infection in Blood and 
Blood Components  
 
 
Guidance for Industry
 
 
 
Additional  copies of this guidance are available from the Office of Communication,  Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002,  or by calling 1-800-835-4709  or 240-402-8010,  or email ocod@fda.hhs.gov, or 
from the Internet at 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guid
ances/default.htm. 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
December 2017 
 
OMB Control No. 0910-0681 
Expiration Date: 7/31/2023 
See additional PRA statement in Section VI of this guidance  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION ...................................................................................................... 1 
II.  BACKGROUND ........................................................................................................ 2 
A.  Blood Donor Testing for Chagas Disease in the United States........................ 2 
B.  Donor Screening for History of Chagas Disease ............................................. 4 
C.  Further Testing of Donations Repeatedly Reactive with a Licensed Screening 
Test for Antibodies to T. cruzi ........................................................................ 4 
D.  Donor Reentry................................................................................................. 5 
III.  RECOMMENDATIONS............................................................................................ 6 
A.  Blood Donor Testing, Deferral, Further Testing and Notification.................. 7 
B.  Reentry Algorithm for Donors Deferred on the Basis of Screening Test 
Results for Antibodies to T. cruzi or Predonation Screening Question .......... 8 
C.  Product Managemen ..................................................................................... 10 
IV.  IMPLEMENTATION .............................................................................................. 11 
A.  Donor Screening............................................................................................ 11 
B.  Reentry of Deferred Donors.......................................................................... 12 
V.  REFERENCES......................................................................................................... 13 
VI.  PAPERWORK REDUCTION ACT OF 1995 .......................................................... 15 
APPENDIX:  REENTRY ALGORITHM FOR DONORS DEFERRED ON THE BASIS 
OF SCREENING TEST RESULTS FOR ANTIBODIES TO T. CRUZI OR 
PREDONATION SCREENING QUESTION............................................... 16 
 
 
i  Contains Nonbinding Recommendations 
Use of Serological Tests to Reduce the Risk of Transmission  of 
Trypanosoma cruzi Infection in Blood and Blood Components 
 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
We, FDA, are providing  you, blood collection  establishments,  with recommendations regarding 
the use of serological  tests to reduce the risk of transmission of Trypanosoma cruzi (T. cruzi) 
infection in blood and blood components.  These recommendations apply to the collection  of 
blood and blood components, except Source Plasma, for transfusion or for use in manufacturing 
a product, including  donations intended as a component of, or used to manufacture, a medical 
device. 
 
FDA previously  issued the following  guidance documents related to T. cruzi: 
 
  In 2010, we issued a document entitled 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 dated December 2010 (2010 Chagas 
Guidance). 
  In 2016, we issued a draft document entitled Amendment to 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; Draft 
Guidance for Industry dated November 2016 (2016 Draft Chagas Guidance). 
 
The 2016 Draft Chagas Guidance, if finalized,  would have amended the 2010 Chagas Guidance 
by:  1) expanding the scope of the guidance to include the collection of blood and blood 
components for use in manufacturing a product, including  donations intended as a component of, 
or used to manufacture, a medical device, 2) removing the recommendation  to ask donors about 
a history of Chagas disease, and 3) providing  a recommendation for a reentry algorithm  for 
certain donors deferred on the basis of screening test results for antibodies to T. cruzi or on the 
basis of answering yes to the Chagas screening question.  The 2016 Draft Chagas Guidance 
also noted that FDA had licensed a supplemental test for antibodies  to T. cruzi and further testing 
of donations found repeatedly reactive to a screening test for T. cruzi is therefore required under 
21 CFR 610.40(e). 
1  Contains Nonbinding Recommendations 
 
This guidance supersedes the 2010 Chagas Guidance and finalizes  the 2016 Draft Chagas 
Guidance.   
 
T. cruzi is a relevant transfusion-transmitted  infection (RTTI) (21 CFR 630.3(h)(1)(vii)),  and 
therefore subject to the testing requirements in 21 CFR 610.40, the donor deferral practices in  
21 CFR 610.41, and the donor notification  requirements in 21 CFR 630.40.1 
 
FDAs guidance documents, including  this guidance, do not establish legally  enforceable 
responsibilities.   Instead, guidances describe FDAs 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 FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
Chagas disease is caused by the protozoan parasite T. cruzi.  The disease is endemic in Mexico 
and Central and South America.  Natural infections are transmitted by infected blood sucking 
insects (triatomine bugs).  Several cases of natural transmission  also have been reported in the 
United States (U.S.), which were associated with documented infections in insect vectors and 
reservoir hosts in the southern U.S. (Refs. 1 and 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 can be very serious and sometimes 
fatal.  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.  Treatment options are limited,  and are most effective early in 
the infection.  During the chronic phase of Chagas disease, most persons are asymptomatic and 
unaware of their infection.  During this phase, parasites have been identified  on examination  of 
muscle (especially cardiac muscle), nerves, and the digestive tract.  However, there has been 
little investigation  into the mechanisms that trigger mobilization  of parasites that can be present 
into the circulating  blood during the chronic phase (Refs. 3 through 5). 
 
Other known routes of transmission  include oral, congenital  (mother to unborn infant), organ 
transplantation  and blood transfusion.  The presence of the pathogenic agent in U.S. donors has 
increased due to immigration  of infected individuals  from endemic areas.  Some experts estimate 
that approximately  300,000 persons unknowingly  infected with T. cruzi reside in the U.S. (Ref. 
6).  These individuals  could serve as a potential source of transfusion-transmitted  infection 
should they become U.S. donors.  In the U.S. and Canada, 10 cases of transfusion-transmitted  T. 
cruzi and 9 cases of infection from organ transplantation have been documented (Refs. 7 through 
9). 
 
A.  Blood Donor Testing for Chagas Disease in the United States 
                                                             
1 See Requirements for Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use; 
Final Rule (80 FR 29842, May 22, 2015), effective May 23, 2016. 
2  Contains Nonbinding Recommendations 
 
The voluntary testing of U.S. blood donors for antibodies  to T. cruzi was initiated  in 
January 2007, subsequent to FDA licensure of the first T. cruzi blood donor screening 
test.2  A second serological test for detection of antibodies to T. cruzi in donors was 
licensed on April 30, 2010.3 
 
At the April 2009 Blood Products Advisory Committee (BPAC) meeting, FDA sought 
advice from the committee regarding selective testing strategies for T. cruzi infection in 
repeat blood donors.  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 
potential testing strategies, 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 questions regarding risk of a newly acquired infection 
(Ref. 10).  The committees recommendation  was contingent upon the continuation  of 
studies to define the incidence of new infections in previously  screened negative donors. 
 
In the 2010 Chagas Guidance, FDA recommended one-time testing of each donor of 
blood and blood components intended for transfusion using a licensed test for antibodies 
to T. cruzi.  The guidance stated that donors who test non-reactive are qualified  to return 
to donate without further testing of subsequent donations for antibodies to T. cruzi and 
that each blood establishment  should review its records to determine the history of testing 
for T. cruzi in prospective donors to determine whether a donor should be tested. 
 
Results of an incidence study were discussed at the August 2, 2011 BPAC meeting.  
Based on the finding  of zero incident cases of T. cruzi infection identified  in over 4.2 
million  donors over 4 years, BPAC recommended that one-time donor testing should 
continue (Ref. 11). 
 
In 2015 (80 FR 29842), FDA defined T. cruzi as a RTTI (21 CFR 630.3(h)(1)(vii))  and, 
as of May 23, 2016, blood establishments must test for T. cruzi consistent with the 
requirements in 21 CFR 610.40, subject to the exceptions found in 21 CFR 610.40(c) and 
(d).  Additionally,  consistent with 21 CFR 610.40(a)(2)(iii)(A),  FDA recommends one-
time testing of each donor blood and blood components using a licensed test for 
antibodies to T. cruzi. 
 
An online report of the AABB Chagas Biovigilance  Network (http://www.aabb.org) 
dated March 14, 2017, showed that between January 1, 2007 and December 31, 2016, 
12,525 donors gave collections that were repeatedly reactive on a licensed screening test 
for antibodies  to T. cruzi.  Of those collections,  2,207 (17.6%) were reported as 
confirmed, 9,596 (76.6%) negative, 684 (5.5%) indeterminate,  and 38 (0.3%) were 
pending at the time the report was generated. 
                                                             
2 ORTHO T. cruzi ELISA Test System, Ortho-Clinical Diagnostics, Inc., Raritan, NJ. 
3 ABBOTT PRISM Chagas, Abbott Diagnostics, Abbott Park, IL. 
3  Contains Nonbinding Recommendations 
 
B.  Donor Screening for History of Chagas Disease 
 
FDAs 2010 Chagas Guidance recommended asking the question Have you ever had 
Chagas disease? to all donors at each donation,  to identify  donors with a history of 
Chagas disease.  It also recommended that donors who answer no to the question 
should be tested with a licensed screening test for antibodies  to T. cruzi, and donors who 
answer yes to this question should be deferred indefinitely  and notified  of their 
deferral.  In a recent study, Steele, et al., identified  34 donors deferred because of a 
history of Chagas disease as revealed by the question among approximately  76 million 
qualified  donors screened by the American Red Cross (ARC) between January 2000 and 
August 2011 (Ref. 12).  In comparison,  ARC identified  488 donations positive by the 
unlicensed supplemental  Radioimmunoprecipitation  Assay (RIPA) among approximately 
21 million  donations tested between January 2007 and August 2011.  The 488 T. cruzi 
RIPA positive donors had not responded in the affirmative to the Chagas history question 
during the predonation screening process.  This report also showed that only one of the 
six donors who provided a follow-up  sample, among the 34 donors deferred based on the 
Chagas disease history question,  had a repeatedly reactive result with a licensed 
screening test.  This donor was also T. cruzi RIPA positive on further testing.  The 
authors concluded that the Chagas question has no added value when all donors are tested 
at least once. 
 
Based on the low sensitivity  and specificity  of the donor question, the significant  clinical 
sensitivity  of the two currently licensed screening tests (Refs. 13 and 14), the low (0.8%) 
risk of transfusion-transmitted T. cruzi infection from a seropositive  donor (Ref. 11), and 
the observation that T. cruzi RIPA positive donors are likely  not aware of their infection, 
we are recommending  that one-time testing alone, without donor questioning  for history 
of Chagas disease, is adequate and appropriate to identify donors at risk for transmission 
of Chagas disease. 
 
C.  Further Testing of Donations Repeatedly Reactive with a Licensed Screening 
Test for Antibodies to T. cruzi 
 
Consistent with 21 CFR 610.40(e), you must further test each donation  found to be 
reactive by a donor screening test using a licensed, approved or cleared supplemental  test, 
when available.4  In November 2011, FDA licensed a supplemental  test for antibodies to 
T. cruzi.5  This test is intended for use as an additional,  more specific test for human 
serum or plasma specimens found to be repeatedly reactive using a licensed screening 
test for antibodies to T. cruzi. 
 
A positive test result on the licensed supplemental  test indicates that antibodies to T. cruzi 
were detected, providing  further confirmation  of the repeatedly reactive licensed 
screening test result.  Conversely, scientific data support FDAs current thinking  that 
donors whose blood samples are found to be repeatedly reactive on a licensed screening 
                                                             
4 See footnote 1. 
5 ABBOTT ESA Chagas, Abbott Diagnostics, Abbott Park, IL. 
4  Contains Nonbinding Recommendations 
test, but negative on a licensed supplemental  test, may be considered for reentry as set 
forth in section III.B of this document. 
 
D.  Donor Reentry 
 
The reentry of donors deferred on the basis of screening test results for antibodies to T. 
cruzi was discussed at the July 31, 2014 BPAC meeting (Ref. 15). 
 
FDA presented an analysis of donor follow-up  studies used to develop a proposed donor 
reentry algorithm  and four alternative scenarios.  In these follow-up  studies, donors 
whose collections  were repeatedly reactive on a licensed screening test for antibodies  to 
T. cruzi and negative on a licensed supplemental test for antibodies  to T. cruzi on their 
initial  donation were further evaluated to determine their eligibility  for reentry as donors.  
Follow-up  testing was performed to assess their most likely  T. cruzi infection status and 
determine those who could safely be reentered. 
 
Results of the follow-up  studies showed that 117/238 (49.2%) of donors in the FDA 
analysis had follow-up  samples that were non-reactive with the two licensed screening 
tests.  Among the 117 donors with negative screening tests on follow-up,  115/117 
(98.3%) had non-reactive results with the licensed supplemental  test.  Conversely, 2/117 
(1.7%) of these donors had indeterminate results with the licensed supplemental  test. 
These studies showed that testing the follow-up  samples with only the two licensed 
screening tests did not identify  all the donors with antibody reactivity to T. cruzi antigens. 
 
FDA believes that it would not be safe to reenter a donor with any reactivity with a 
licensed supplemental  test given the higher analytical sensitivity  of the currently licensed 
supplemental  test compared with the licensed screening tests and the consequent 
uncertainty regarding the donors infectious status.  FDA considers donors whose follow-
up samples are tested with all three currently licensed tests and show no reactivity with 
any of the three tests to be eligible  for reentry, provided all other donor eligibility  criteria 
are met.  A least burdensome approach to identifying  potentially  eligible  donors would be 
to perform sequential testing.  The donors follow-up  samples would be first tested with 
the two licensed screening tests, which are run on automated instruments.  Only 
specimens which are non-reactive on both screening tests would be subsequently tested 
with the manual licensed supplemental  test. 
 
Previously deferred donors who have had positive  test results with either the unlicensed 
T. cruzi RIPA test or with an investigational  or licensed supplemental  test for antibodies 
to T. cruzi are not eligible  for reentry and therefore should not be considered for reentry 
using the recommended algorithm  (see section III.B and Appendix of this document).  
The T. cruzi RIPA test has a long history of use to identify individuals  infected with T. 
cruzi.  In a study by ARC of T. cruzi RIPA positive donors, 74.5% (117/157),  were born 
in a T. cruzi endemic country (Ref. 10).  Data from the licensed supplemental  test clinical 
trial showed high concordance, 98.7% (151/153), between T. cruzi RIPA positivity  and 
licensed supplemental  test positivity  among screening test repeatedly reactive donors 
(Ref. 16).  Similarly,  previously  deferred donors who have had an indeterminate test 
5  Contains Nonbinding Recommendations 
result with either the T. cruzi RIPA test or with an investigational  or licensed 
supplemental  test are not eligible  for reentry and therefore should not be considered for 
reentry using the recommended algorithm.   As noted in section II.A of this guidance, 
these donors represent a small percentage (5.5%) of currently deferred donors and 
because their infectious status is unclear due to low level antibody reactivity to T. cruzi 
specific antigens, FDA considers them not eligible  for reentry.6  Only previously deferred 
donors with negative test results on the unlicensed T. cruzi RIPA (if so tested) and the 
investigational  or licensed supplemental  test for antibodies to T. cruzi  (if so tested), and 
deferred donors who have never been tested by T. cruzi RIPA or an investigational  or 
licensed supplemental  test should be considered for reentry using the recommended 
algorithm. 
 
Deferred donors who previously  answered yes to the predonation  screening Chagas 
question may also be considered for reentry using the recommended algorithm  provided 
that they have had no positive or indeterminate test results on the unlicensed T. cruzi 
RIPA or on the investigational  or licensed supplemental  test for Chagas.7 
 
Donors who may be considered for reentry using the recommended algorithm  may 
provide a follow-up  blood sample for testing after a minimum  of 6 months since the time 
of their last deferral.  Although all T. cruzi positive U.S. blood donors identified  since 
testing was initiated  January 2007 have shown evidence of a long term rather than recent 
infection,  the six-month time period prior to reentry testing would add a safeguard by 
allowing  time for maturation of an early antibody response in a donor with low level 
antibodies at the index donation due to recent infection.  Six months would also allow for 
potential resolution  of cross-reacting antibodies  attributable to an unrelated acute medical 
condition  that may have produced the repeatedly reactive screening test result. 
 
While the BPAC did not take a formal vote on the donor reentry algorithm  proposed by 
FDA at its July 31, 2014 BPAC meeting, the Committee discussed this approach and did 
not express concerns about the adequacy of this plan as a reentry algorithm  (Ref. 15). 
 
 
III.  RECOMMENDATIONS  
 
These recommendations apply to the collection of blood and blood components, except Source 
Plasma, for transfusion or for use in manufacturing a product, including  donations  intended as a 
component of, or used to manufacture, a medical device.8 
 
                                                             
6 FDA may reconsider in the future the eligibility of donors with an indeterminate test result using the unlicensed T. 
cruzi RIPA test, or an investigational or licensed supplemental test for antibodies to T. cruzi based on newly 
acquired supporting scientific evidence that these donors are not infected. 
7 If donors participated in follow-up studies prior to May 23, 2016, those with a positive or indeterminate test result 
with an investigational or licensed supplemental test for antibodies to T. cruzi or with the unlicensed T. cruzi RIPA 
test should not be considered eligible for reentry. 
8 Blood establishments are not required to test donations of Source Plasma for evidence of infection due to T. cruzi 
(21 CFR 610.40(a)(2)(ii)). 
6  Contains Nonbinding Recommendations 
We no longer recommend that the question Have you ever had Chagas disease? be asked to all 
donors at each donation.  The question may be removed from your donor history questionnaire. 
Donors deferred previously  on the basis of answering yes to the predonation  screening 
question Have you ever had Chagas disease? may be considered for reentry as described in 
section III.B of this document. 
 
A.  Blood Donor Testing, Deferral, Further Testing and Notification 
 
1.  Donor Testing 
 
You must test donations for evidence of T. cruzi using a licensed screening test 
for antibodies  to T. cruzi (21 CFR 610.40(a)(2)), subject to the exceptions found 
in 21 CFR 610.40(c) and (d).  We recommend one-time testing of each donor of 
blood and blood components (21 CFR 610.40(a)(2)(iii)(A)).   We also recommend 
one-time testing of autologous  donors of blood and blood components only when 
the circumstances described in 21 CFR 610.40(d)(1) through (3) are applicable. 
 
Each blood establishment should review its records9 to determine the history of 
testing for T. cruzi in prospective donors to determine whether a donor should be 
tested. 
 
Donors who test non-reactive are qualified  to return for subsequent donations 
without further testing of subsequent donations for antibodies to T. cruzi. 
 
2.  Donor Deferral, Further Testing and Notification 
 
Donors who test repeatedly reactive on a licensed screening test for T. cruzi 
antibody must be deferred (21 CFR 610.41(a)). 
 
You must further test each donation which tests repeatedly reactive using a 
licensed screening test for antibodies to T. cruzi with a licensed, approved, or 
cleared supplemental  test for antibodies to T. cruzi (See 21 CFR 610.40(e)).  
Further, you must make reasonable attempts to notify any donor that tests 
repeatedly reactive for antibodies to T. cruzi of their deferral and of their test 
results including  the results of further testing required under 21 CFR 610.40(e) 
within 8 weeks after determining  that the donor is deferred (See 21 CFR 630.40). 
 
Donors whose blood tests positive  or indeterminate on the licensed supplemental 
test should be deferred permanently and informed of the likelihood  and medical 
significance of infection  with T. cruzi.  Donors whose blood tests negative on a 
licensed supplemental  test may be considered for reentry using the recommended 
algorithm  and informed of the procedure to follow for reentry. 
 
 
                                                             
9 Blood establishments are required to maintain donor and processing records under 21 CFR 606.160. 
7  Contains Nonbinding Recommendations 
B.  Reentry Algorithm for Donors Deferred on the Basis of Screening Test 
Results for Antibodies to T. cruzi or Predonation Screening Question 
 
We consider the recommendations for donor reentry in this section to be an acceptable 
requalification  method or process, within the meaning of 21 CFR 610.41(b),  for reentry 
of donors deferred due to repeatedly reactive screening tests for antibodies to T. cruzi and 
within the meaning of 21 CFR 630.35(b)10 for donors deferred for previously  answering 
yes to the donor history question, Have you ever had Chagas disease? 
 
1.  FDA recommends that donors with the following  Chagas test results are 
not eligible  for reentry.11 
 
a.  Positive or indeterminate  with an investigational  or licensed 
supplemental  test for antibodies to T. cruzi. 
 
OR 
 
b.  Positive or indeterminate  with the unlicensed T. cruzi RIPA test. 
 
2.  Donors deferred on the basis of screening test results for antibodies  to T. 
cruzi who had (at the time of donation that prompted the deferral) the 
following  Chagas test results may be considered for reentry provided that 
they do not meet any of the ineligibility  criteria described in item 1 of this 
section:11 
 
a.  Negative with an investigational  or licensed supplemental  test for 
antibodies to T. cruzi. 
 
OR 
 
b.  Negative with the unlicensed T. cruzi RIPA test. 
 
OR 
 
c.  Not tested with an investigational  or licensed supplemental test for 
antibodies to T. cruzi, and not tested with the unlicensed T. cruzi RIPA 
test. 
 
3.  Donors deferred previously on the basis of answering yes to the 
predonation screening question Have you ever had Chagas disease? may 
                                                             
10 See footnote 1. 
11 Effective May 23, 2016, blood collection establishments must use a licensed supplemental test for T. cruzi in 
accordance with 21 CFR 610.40(e). 
8  Contains Nonbinding Recommendations 
also be considered for reentry provided that they do not meet any of the 
ineligibility  criteria described in item 1 of this section.12,13 
 
4.  To reenter a donor who meets the criteria described in items 2 or 3 of this 
section, we recommend that you do the following  (see also algorithm  in 
the Appendix): 
 
a.  At least 6 months after the date of deferral, obtain a new blood sample 
from the donor (no donation  is made at this time) and perform follow-
up testing as follows: 
 
i.  Test sample using two different licensed screening tests for 
antibodies to T. cruzi. 
 
One of the two screening tests should be the test that was 
repeatedly reactive on the original  donation. 
 
AND 
 
ii.  If the follow-up  sample is non-reactive with the two licensed 
screening tests, then test the follow-up  sample with a licensed 
supplemental  test for antibodies to T. cruzi. 
 
b.  Evaluate the results of the follow-up testing on the donors new 
sample as follows: 
 
i.  If either one or both screening tests are repeatedly reactive, we 
recommend that you defer the donor permanently. 
 
ii.  If the licensed supplemental test is either positive or 
indeterminate,  we recommend that you defer the donor 
permanently. 
 
iii. If the two licensed screening tests are non-reactive and the 
licensed supplemental  test is negative, you may reenter the 
donor provided all other donor eligibility  criteria are met at the 
time of donation.  Testing for T. cruzi is not required on future 
blood donations from the reentered donor. 
 
   
                                                             
12 If donors participated in follow-up studies prior to May 23, 2016, those with a positive or indeterminate test result 
with an investigational or licensed supplemental test for antibodies to T. cruzi or with the unlicensed T. cruzi RIPA 
test should not be considered eligible for reentry. 
13 We no longer recommend that donors be asked the question Have you ever had Chagas disease? 
9  Contains Nonbinding Recommendations 
C.  Product Management 
 
1.  Index Donations 
 
You must not ship or use blood and blood components that test repeatedly 
reactive for antibodies  to T. cruzi unless an exception exists (21 CFR 610.40(h) 
and 21 CFR 630.30(b)(1)).  You must appropriately  label such blood or blood 
components as required under 21 CFR 606.121 and with the BIOHAZARD 
legend (21 CFR 610.40(h)(2)(ii)(B).   Blood and blood components determined to 
be unsuitable for transfusion must be prominently  labeled: NOT FOR 
TRANSFUSION, and the label must state the reason the unit is considered 
unsuitable.  This requirement does not apply to blood and blood components 
intended solely for further manufacture (21 CFR 606.121(f)). 
 
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: 
 
a.  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 donors most recent negative test result with a 
licensed test for T. cruzi antibody, whichever is the lesser period (the 
lookback period).  It is recognized that under the selective testing 
recommended herein, most donors tested will not have a prior negative 
test. 
 
b.  Quarantine all previously  collected in-date blood and blood 
components from that donor held at your establishment; and 
 
c.  Notify consignees of all previously  collected in-date blood and blood 
components from that donor 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 
screening test for T. cruzi and positive or indeterminate by a licensed or 
investigational  supplemental  test, we recommend that you: 
 
d.  Notify consignees of all previously  distributed blood and blood 
components collected from that donor during the lookback period; and 
 
e.  If blood or blood components were transfused, encourage consignees 
to notify the recipients physician of record of a possible increased risk 
of T. cruzi infection. 
 
10  Contains Nonbinding Recommendations 
f.  Make such notifications  within 12 weeks of obtaining  the repeatedly 
reactive test result. 
 
3.  Autologous  Donation 
 
Although autologous  use of blood does not increase a patients/donors  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.  Additionally, 
 
a.  Establishments  must provide the results of further testing under  
21 CFR 610.40(e) to the autologous  donors referring physician. (21 
CFR 630.40(d)(1)(iii)  and (d)(2)). 
 
b.  Each autologous donation must be labeled as required under  
21 CFR 610.40(d)(4) and 21 CFR 606.121(i)(5),  as appropriate.  
Autologous  donations that are repeatedly reactive by a licensed test for 
T. cruzi antibody must bear a BIOHAZARD legend.  See 21 CFR 
610.40(d)(4). 
 
4.  Circular of Information 
 
Under 21 CFR 606.122(h),  the circular of information  must include the names and 
results of all tests performed when necessary for safe and effective use.  We 
recommend the following  statement for T. cruzi testing: 
 
All blood has been collected from donors who have tested negative by a 
licensed test for antibodies to Trypanosoma cruzi either on the current 
donation or at least one previous donation. 
 
 
IV.  IMPLEMENTATION  
 
A.  Donor Screening 
 
If you are a licensed establishment  and you remove the Have you ever had Chagas 
disease? question from your donor history questionnaire  (DHQ), you must report this 
change to FDA under 21 CFR 601.12, as follows:14 
1.  Revision of your own DHQ and accompanying materials:  report in your 
annual report consistent with 21 CFR 601.12(d),  noting the date the 
question was removed from your DHQ and accompanying materials. 
 
                                                             
14 See 21 CFR 601.12(a)(3). 
11  Contains Nonbinding Recommendations 
2.  Revision of a previously  FDA accepted DHQ and accompanying 
materials:  report in your annual report consistent with 21 CFR 601.12(d), 
noting the date the question was removed from the accepted DHQ and 
accompanying materials. 
 
Unlicensed establishments are not required to report this change to FDA but are required 
to maintain  records under 21 CFR 606.160. 
 
B.  Reentry of Deferred Donors 
 
We consider the recommendations  in section III.B of this document for donor reentry to 
be an acceptable requalification  method or process, within the meaning of 21 CFR 
610.41(b), for reentry of donors deferred due to repeatedly reactive screening tests for 
antibodies to T. cruzi and within the meaning of 21 CFR 630.35(b)15 for donors deferred 
for previously  answering yes to the donor history question,  Have you ever had Chagas 
disease? 
 
Licensed establishments implementing  the recommendations for donor reentry in this 
guidance must report this change to FDA as required under 21 CFR 601.12.  Specifically, 
licensed establishments must submit a statement of this change in an annual report under 
21 CFR 601.12(d), indicating  the date that the revised standard operating procedures 
were implemented  (see 21 CFR 601.12(a)(3)).  Unlicensed establishments implementing 
the recommendations for donor reentry in this guidance in their entirety and without 
modification  are not required to report this change to FDA. 
 
Sections 610.41(b) and 630.35(b) require that a donor requalification  method or process 
used to requalify a donor be acceptable to FDA.  Accordingly,  before you implement  an 
alternative requalification  method or process from that described in this guidance, FDA 
must first find the alternative method or process to be acceptable for such purpose.  
Licensed establishments intending  to use an alternative requalification  method must 
submit a supplement for prior approval, as required under 21 CFR 601.12(b).  Similarly, 
before an unlicensed establishment implements  an alternative requalification  method or 
process from that described in this guidance, FDA must first find the method or process 
to be acceptable for such purpose (21CFR 610.41(b) and 630.35(b)). 
                                                             
15 See footnote 1. 
12  Contains Nonbinding Recommendations 
V.  REFERENCES 
 
1.  Dorn P. L., et al., Autochthonous  transmission of Trypanosoma cruzi, Louisiana. 
Emerg Infect Dis 13(4): 605-607 (2007). 
 
2.  Garcia, M. N., et al., Case Report:  Evidence of Autochthonous Chagas Disease in 
Southeastern Texas. Am J Trop Med Hyg 92(2): 325-330 (2015). 
 
3.  Vago, A. R., et al., PCR detection of Trypanosoma cruzi DNA in oesophageal tissues of 
patients with chronic digestive Chagas disease. Lancet 348: 891-892 (1996). 
 
4.  Anez, N., et al., Myocardial parasite persistence in chronic chagasic patients. Am J 
Trop Med Hyg 60(5): 726-732 (1999). 
 
5.  Virreira, M., et al., Trypanosoma cruzi:  Typing of genotype (sub)lineages in megacolon 
samples from bolivian  patients. Acta Tropica 100(3): 252-255 (2006). 
 
6.  Manne-Goehler, J., et al. Estimating  the Burden of Chagas Disease in the United 
States. PLoS Negl Trop Dis 10(11): e0005033 (2016). 
 
7.  Benjamin,  R. J., et al., Trypanosoma cruzi infection in North America and Spain: 
evidence in support of transfusion transmission. Transfusion 52: 1913-1921  (2012). 
 
8.  Kirchhoff, L.V. Epidemiology  of American trypanosomiasis  (Chagas disease). Adv 
Parasitol 75: 1-18 (2011). 
 
9.  Huprikar, S., et al., Donor-Derived Trypanosoma cruzi Infection in Solid Organ 
Recipients in the United States, 20012011. American Journal of Transplantation  13: 
2418-2425 (2013). 
 
10.  FDA Blood Products Advisory Committee Potential Testing Strategies for T. cruzi 
Infection in Blood Donors. April 1, 2009.  Available at https://wayback.archive-
it.org/7993/20170111183035/http://www.fda.gov/AdvisoryCommittees/CommitteesMeet
ingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm2
76273.htm. 
 
11.  FDA Blood Products Advisory Committee T. cruzi Incidence Study in Blood Donors 
and its Implications  for One-time Testing of Blood Donors. August 2, 2011.  Available 
at https://wayback.archive-
it.org/7993/20170111183050/http://www.fda.gov/AdvisoryCommittees/CommitteesMeet
ingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm2
88494.htm.  
 
12.  Steele, W. R., et al., Donors deferred for self-reported Chagas disease history: does it 
reduce risk? Transfusion 54(8): 2092-2097  (2014). 
 
13  Contains Nonbinding Recommendations 
13.  Trypanosoma cruzi (T. cruzi) Whole Cell Lysate Antigen, ORTHO T. cruzi ELISA Test 
System, Package Insert (2009).  Available at 
https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/L
icensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm085846.htm. 
 
14.  Trypanosoma cruzi (E. coli, Recombinant) Antigen, ABBOTT PRISM Chagas, Package 
Insert (2010).  Available at 
https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/L
icensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm210158.htm#. 
 
15.  FDA Blood Products Advisory Committee Reentry of blood donors deferred on the 
basis of screening test results for antibodies to T. cruzi. July 31, 2014.  Available at 
https://wayback.archive-
it.org/7993/20170111180042/http://www.fda.gov/AdvisoryCommittees/CommitteesMeet
ingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm3
86681.htm.  
 
16.  Trypanosoma cruzi (E. coli, Recombinant) Antigen, ABBOTT ESA Chagas, Package 
Insert (2011).  Available at 
https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/L
icensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm280719.htm. 
 
 
14  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. 
3501-3520).  The collections  of information  that the establishment notify consignees of all 
previously  collected in-date blood and blood components to quarantine and return the blood and 
blood components to establishments or to destroy them; notify consignees of all previously 
distributed  blood and blood components collected during the lookback period; encourage 
consignees to notify the recipients physician of record of a possible increased risk of T. cruzi 
infection; and provide the results of further testing to the autologous  donors referring physician 
do not create a new burden for respondents and are part of usual and customary business. 
 
This guidance also refers to previously  approved collections  of information  found in FDA 
regulations.  The collections  of information  in 21 CFR part 601 have been approved under OMB 
control number 0910-0338;  and the collections  of information  in 21 CFR parts 606, 610, and 630 
have been approved under OMB control number 0910-0116.   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 0910-0681 (expires7/31/2023). 
15  Contains Nonbinding Recommendations 
APPENDIX:  Reentry Algorithm for Donors Deferred on the Basis of Screening Test 
Results for Antibodies to T. cruzi or Predonation Screening Question 
 
Deferred donors that meet the following conditions and do not meet the 
 
ineligibility criteria described in this guidancea,b: 
 
  Negative (at the time of the donation that prompted the deferral) with an 
 
investigational or licensed supplemental test for antibodies to T. cruzi; or  
 
  Negative (at the time of the donation that prompted the deferral) with the 
 
unlicensed T. cruzi RIPA test; or  
    Not tested (at the time of the donation that prompted the deferral) with an 
  investigational or licensed supplemental test for antibodies to T. cruzi or with the 
  unlicensed T. cruzi RIPA test; or  
    Deferred on the basis of answering yes to the predonation Chagas questionc 
 
 
 
 
Obtain a follow-up sample > 6 
 
months since date of deferral  
  RR on either 
test or RR on 
 
both tests  
 
Defer donor 
  Test follow-up sample with two  Permanently  
  different licensed screening tests  
 
  NR on both tests  
  POS or IND  
Test follow-up sample with a 
 
licensed supplemental test  
 
 
NEG  
 
 
Reenter donor provided all other 
 
donor eligibility criteria are met. 
 
Testing for T. cruzi antibodies is 
 
not required on future blood 
 
donations from the reentered 
  donor.  
 
RR = repeatedly reactive; NR = non-reactive; POS = positive; NEG = negative; IND = indeterminate 
 
a Effective May 23, 2016, blood collection establishments must use a licensed supplemental test for T. cruzi  
in accordance with 21 CFR 610.40(e).   
b FDA recommends that donors with the following Chagas test results are not eligible for reentry:  (1) Positive or 
indeterminate with an investigational or licensed supplemental test for antibodies to T. cruzi or (2) Positive or 
indeterminate with the unlicensed T. cruzi RIPA test. 
c If donors participated in follow-up studies prior to May 23, 2016, those with a positive or indeterminate test result 
with an investigational or licensed supplemental test for antibodies to T. cruzi or with the unlicensed T. cruzi RIPA 
test should not be considered eligible for reentry. 
 
16