Recommendations for Reducing the 
Risk of Transfusion-Transmitted 
Babesiosis 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., 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 
May 2019 
  Contains Nonbinding Recommendations 
 
Table of Contents  
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 1 
III.  DISCUSSION .................................................................................................................... 2 
A.  Transfusion-Transmitted Infection ..................................................................... 2 
B.  Relevant Transfusion-Transmitted Infection ..................................................... 3 
IV.  PUBLIC WORKSHOP AND ADVISORY COMMITTEE MEETINGS ON RISK 
MITIGATION FOR TTB ................................................................................................ 5 
V.  RECOMMENDATIONS .................................................................................................. 6 
A.   Donation Testing, Donor History Questionnaire, Donor Deferral and 
Requalification ...................................................................................................... 6 
B.  Product Management, Retrieval and Quarantine, Notification of Consignees 
of Blood and Blood Components ......................................................................... 9 
C.  Product Disposition and Labeling ..................................................................... 10 
D.  Circular of Information ...................................................................................... 11 
VI.  IMPLEMENTATION AND REPORTING CHANGES UNDER 21 CFR 601.12 ... 12 
A.  Donor History Questionnaire............................................................................. 12 
B.  Testing .................................................................................................................. 12 
C.  Circular of Information ...................................................................................... 13 
VII.  REFERENCES ................................................................................................................ 14 
 
 
 
i  Contains Nonbinding Recommendations 
 
Recommendations for Reducing the Risk of Transfusion-
Transmitted Babesiosis  
 
 
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, the Food and Drug Administration (FDA), are notifying you, blood establishments that 
collect blood and blood components, that we have determined babesiosis to be a relevant 
transfusion-transmitted infection (RTTI) under 21 CFR 630.3(h)(2).1  Accordingly, we are 
providing recommendations for donor screening, donation testing, donor deferral and product 
management to reduce the risk of transfusion-transmitted babesiosis (TTB).  The 
recommendations contained in this guidance apply to the collection of blood and blood 
components, except Source Plasma.2  
 
This guidance finalizes the draft guidance of the same title dated July 2018.   
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidance documents describe the Agencys 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 Agency guidance means that something is 
suggested or recommended, but not required. 
 
 
II.  BACKGROUND 
 
Human babesiosis is a tick-borne zoonosis caused by infections of humans with intra-
erythrocytic protozoa of the genus Babesia.  Babesiosis can also be transmitted by transfusion of 
blood and blood components (Refs. 1, 2) and by transplantation of solid organs (Ref. 3) collected 
                                                 
1 See Requirements for Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use; 
Final Rule (80 FR 29842, May 22, 2015).  The rule became effective May 23, 2016. 
2 Source Plasma is used for further manufacture of plasma-derived products.  Pathogen inactivation and removal 
methods that are currently used in the manufacturing process for plasma-derived products are sufficient to reduce 
the risk of Babesia transmission.   
 
1  Contains Nonbinding Recommendations 
from an infected donor.  Babesiosis is transmitted in many parts of the world but the highest 
prevalence is reported in the United States (U.S.).  The first documented human case of 
babesiosis in the U.S. was identified in 1968 (Ref. 4).  The vast majority of U.S. babesiosis cases 
are caused by B. microti, the species that is prevalent in the Northeast and upper Midwest (Ref. 
5).  Less commonly, other Babesia species such as B. duncani (Refs. 6, 7) and related organisms 
are implicated in transmission of Babesia in several western U.S. states, while transmission of 
Babesia by B. divergens-like agents (Ref. 8) have been reported in multiple U.S. states. 
 
Most cases of B. microti infections are asymptomatic and never diagnosed (Ref. 9).  While the 
duration of B. microti infections in healthy adults is not precisely known, in limited studies, the 
parasitemic period is reported to last from 2 to 7 months (Ref. 10), but parasitemia may persist 
for more than 2 years (Ref. 11).  In a study of asymptomatic blood donors who were reactive for 
B. microti using investigational nucleic acid tests (NAT) and antibody tests, follow-up testing 
demonstrated DNA clearance in 86% (48 of 56 donors) after 1 year, and 95% (53 of 56 donors) 
after 2 years (Ref. 10).  Babesia transmission is generally seasonal and coincides with tick 
activity (traditionally May-September) in affected states, but tick-borne (Refs. 12-17) and 
transfusion-transmitted infections are reported throughout the year (Ref. 9).  Transfusion of 
blood and blood components collected from asymptomatic infected donors may result in TTB, 
leading to potentially fatal clinical illness in blood transfusion recipients. 
 
 
III.  DISCUSSION 
 
FDA has determined, as discussed below, that babesiosis is a transfusion-transmitted infection 
(TTI) under 21 CFR 630.3(l) and an RTTI under 21 CFR 630.3(h)(2).  This determination is 
based on the severity of the disease, confirmed transfusion-transmission by blood and blood 
components, the availability of appropriate screening measures and donor screening tests and 
significant incidence and prevalence affecting the potential donor population. 
 
A.  Transfusion-Transmitted Infection  
 
A transfusion-transmitted infection (21 CFR 630.3(l)) means a disease or agent: 
 
(1) That could be fatal or life-threatening, could result in permanent impairment 
of a body function or permanent damage to a body structure, or could 
necessitate medical or surgical intervention to preclude permanent impairment 
of body function or permanent damage to a body structure; and  
 
(2)  For which there may be a risk of transmission by blood or blood components, 
or by a blood derivative product manufactured from blood or blood 
components, because the disease or disease agent is potentially transmissible 
by that blood, blood component, or blood derivative product. 
 
  2  Contains Nonbinding Recommendations 
In this regard, FDA examined:  
 
Severity of Disease 
 
Clinical symptoms of babesiosis, caused by B. microti, range from asymptomatic or mild 
to severe, and can result in death, particularly in certain high-risk populations.  In the 
majority of individuals who develop illness, clinical symptoms appear 1 to 4 weeks after 
an infectious tick bite (Ref. 5).  Common symptoms include fever, chills, body aches, 
weakness, malaise and fatigue (Refs. 5, 9, 18, 19).  Severe disease caused by B. microti 
infection requiring hospitalization is generally seen in neonates, the elderly, asplenic 
patients, and those receiving immunosuppressive drugs for cancer therapy (Refs. 5, 19, 
20).  The most common severe clinical manifestations include acute respiratory distress 
syndrome and disseminated intravascular coagulopathy.  Congestive heart failure, coma, 
liver failure and renal failure are also reported (Refs. 5, 19, 20).  In tick-borne cases, 
fatality rates range from 6 to 9% among hospitalized patients and up to 21% in 
immunosuppressed patients (Refs. 19, 20).  In TTB cases, a fatality rate of about 20% has 
been reported in the literature (Ref. 21). 
 
Transfusion Transmission 
 
Babesiosis can be transmitted by transfusion of blood and blood components, with the 
first U.S. case of TTB reported in 1980 (Refs. 1, 2).  Since then, more than 200 TTB 
cases have been documented (Refs. 2, 22).  While B. microti remains the major causative 
agent, three TTB cases have been attributed to B. duncani (Ref. 2) and one possible case 
to B. divergens in the U.S. (Ref. 23).  Following transfusion of blood components 
collected from an infected donor, symptoms in transfusion recipients have been observed 
anywhere from 1 week to 9 weeks, and as long as 6 months after transfusion (Ref. 2).  
 
In conclusion, FDA has determined that babesiosis is a TTI because it is a disease agent 
that can be fatal or life-threatening and is transmissible by blood or blood components.   
 
B.  Relevant Transfusion-Transmitted Infection 
 
Having determined that babesiosis is a TTI, we outline, below, the criteria establishing 
babesiosis as an RTTI under 21 CFR 630.3(h)(2)(i) and (ii).  
 
An RTTI is a transfusion-transmitted infection not listed in 21 CFR 630.3(h)(1) when the 
following conditions are met: 
 
(1) Appropriate screening measures for the transfusion-transmitted infection have 
been developed and/or an appropriate screening test has been licensed, 
approved, or cleared for such use by the FDA and is available; and 
 
(2) The disease or disease agent: (A) May have significant incidence and/or 
prevalence to affect the potential donor population; or (B) May have been 
  3  Contains Nonbinding Recommendations 
released accidentally or intentionally in a manner that could place potential 
donors at risk of infection. 
 
Availability of Appropriate Screening Measures or Screening Tests 
 
Licensed Screening Tests:  On March 6, 2018, FDA licensed two independent assays for 
screening donors for B. microti:  the Imugen Babesia microti Arrayed Fluorescent 
Immunoassay (AFIA) for the detection of B. microti-specific antibodies and the Imugen 
Babesia microti Nucleic Acid Test (NAT) for the detection of DNA of B. microti.  
However, the manufacturer notified FDA of the permanent discontinuance of both donor 
screening tests in November 2018.  On January 24, 2019, FDA licensed the Grifols 
Procleix Babesia Assay for the detection of RNA from Babesia species (B. microti, B. 
duncani, B. divergens, and B. venatorum) in whole blood specimens for use in screening 
donors of whole blood and blood components.  
 
Pathogen Reduction:  FDA has approved pathogen reduction devices that report effective 
reduction of B. microti for indicated plasma or platelet components in the instructions for 
use, which can be used as an alternative to testing or donor questions.   
 
Donor History Questionnaire (DHQ):  Upon implementing the recommendations in this 
guidance, we do not find it necessary for blood establishments to continue to ask about a 
history of babesiosis using the current question on the DHQ.  Donors implicated in TTB 
cases have been unaware of their infection status and hence have not reported a history of 
babesiosis before donation (Ref. 24).  When testing for Babesia begins according to the 
recommendations in this guidance, we expect that some asymptomatic blood donors will 
learn about their infection status when they are deferred.  However, these donors might 
still present to donate in a state where testing or pathogen reduction is not performed. 
Accordingly, we are recommending a question on the DHQ, as follows:    
 
  If donations are not tested or pathogen reduced, we are recommending a question 
to assess donors for a history of ever having a positive test result for Babesia, 
obtained either from a medical diagnosis or reactive donor screening test.  Such 
donors are not eligible for donation, unless they are requalified by the 
recommendations in this guidance.   
 
  If donations are tested, or if blood components from the donation are pathogen 
reduced using an FDA-approved device effective against Babesia according to the 
instructions for use, we are not recommending any Babesia-related questions.  
However, if establishments choose to continue to ask a Babesia-related question, 
donors with risk should be deferred according to the recommendations in this 
guidance.  
 
Significant Incidence and Prevalence 
 
In 2011, babesiosis became a nationally notifiable disease.  Between 2011 and 2017, an 
average of 1,628 (range 937-2,100) babesiosis cases per year was observed in 26 states, 
  4  Contains Nonbinding Recommendations 
excluding several Babesia-risk states because disease reporting was not required in those 
states (Refs. 12-17).  According to data from the Centers for Medicare and Medicaid 
Services (CMS), babesiosis cases were reported among elderly Medicare beneficiaries in 
all states and Washington, D.C., except for Wyoming (Refs. 25, 26).  In aggregate, more 
than 200 cases of TTB have been documented (Refs. 2, 22, 27).  About 99% of the 
clinical babesiosis cases reported and 95% of TTB cases reported are from Connecticut, 
Massachusetts, Rhode Island, New York, New Jersey, Minnesota, Wisconsin, New 
Hampshire, Maine, Maryland, Virginia, Vermont, Pennsylvania, Delaware, and 
Washington, D.C. (Refs. 12-17, 25, 26). 
 
TTB risk in other states is mostly attributed to infected donors who had lived or traveled 
in Babesia-risk states or to distribution of blood components collected in areas affected 
by Babesia to other states.  
 
In summary, we have determined that babesiosis meets the criteria in 21 CFR 630.3(h)(2) 
for an RTTI because of the availability of appropriate screening measures and screening 
tests, and because of the sufficient incidence and prevalence of Babesia to affect the 
potential donor population in the U.S.  
 
 
IV.  PUBLIC WORKSHOP AND ADVISORY COMMITTEE MEETINGS ON RISK 
MITIGATION FOR TTB 
 
FDA solicited public input on how best to mitigate the risk of TTB in the U.S. and support the 
development of donor screening tests for Babesia.  On September 12, 2008, FDA convened a 
public workshop entitled Approaches to Reduce the Risk of Transfusion-Transmitted 
Babesiosis in the United States (Refs. 28, 29).  The focus of this workshop was to discuss 
various aspects of TTB in the U.S. including the status of detection technologies and possible 
strategies to identify and defer blood donors who might have been exposed to Babesia parasites.  
Experts emphasized the need for better understanding of the epidemiology of babesiosis in the 
U.S. and efforts to develop highly sensitive and specific laboratory tests to identify Babesia-
infected blood donors, especially tests to distinguish between current infections and resolved 
infections.  Discussions also focused on the biology, pathogenesis and epidemiology of 
babesiosis.  A detailed summary of this workshop has been published in Transfusion and the 
meeting transcript is available on the FDA website (Refs. 28, 29). 
 
On July 26, 2010, FDA discussed Risk of Babesia Infection by Blood Transfusion and Potential 
Strategies for Donor Testing at a Blood Products Advisory Committee (BPAC or Committee) 
meeting (Ref. 30).  Based on the information available at that time, the Committee recommended 
regional testing of blood donors for Babesia.  The Committee did not provide advice on the 
question of the most suitable technologies for donor screening for Babesia, noting that additional 
information on the performance of different testing technologies was needed.  A transcript of the 
meeting and the presentations delivered at this BPAC meeting are available on the FDA website 
(Refs. 30-34).  
 
  5  Contains Nonbinding Recommendations 
On May 13, 2015, FDA again sought advice from the BPAC on strategies to test blood donors 
for evidence of B. microti infection using licensed tests, when such tests become available (Ref. 
25).  In recent years, limited testing of blood donations using the available investigational tests 
has provided additional information on the magnitude of B. microti prevalence in endemic areas 
and on the relative value of NAT and antibody-based tests in identifying Babesia-exposed 
donors with resolved infections as opposed to parasitemic donors.  The sponsors of the 
investigational B. microti tests presented the results of their clinical studies (Refs. 35, 36).  The 
Committee advised that the scientific data and FDA analysis support the concept of nationwide, 
year-round testing of blood donations for Babesia risk by an antibody-based test.  The 
Committee also recommended unanimously that NAT-based testing should be performed on 
blood donations in certain high-risk states, and the majority supported NAT testing in the nine 
states considered endemic at that time (i.e., Connecticut, Maine, Massachusetts, Minnesota, New 
Hampshire, New Jersey, New York, Rhode Island, and Wisconsin).  The Committee 
recommended including the bordering state of Pennsylvania in the year-round NAT-based 
testing program.  Additionally, the Committee supported a deferral period of at least 2 years for 
donors with reactive test results, after which time, donor eligibility would be assessed based on 
testing by both antibody and NAT-based testing.  Since the meeting, Pennsylvania has been 
identified as a B. microti endemic state.   
 
FDA considered this BPAC recommendation for testing donations year-round by universal 
antibody testing and regional NAT in states with the highest Babesia risk.  Subsequently, we 
performed an independent risk assessment that determined year-round antibody and NAT testing 
in Babesia-risk states only is a preferred strategy that balances risk reduction with the scope of 
testing.  However, at the time of this writing, a licensed Babesia antibody test is not available for 
blood donor screening.  Consequently, we are recommending regional, year-round testing using 
a licensed NAT for Babesia, or use of an FDA approved pathogen reduction device, in the 
highest risk states.  Consistent with BPACs advice, and based on the available published data on 
Babesia DNA persistence in some screened blood donors beyond one year (Ref. 10), we are 
recommending a 2-year deferral following a reactive donor NAT.   
 
 
V.  RECOMMENDATIONS  
 
A.   Donation Testing, Donor History Questionnaire, Donor Deferral and 
Requalification 
 
The recommendations in this guidance for regional testing for Babesia or pathogen 
reduction of indicated blood components are based on the current epidemiological data 
on Babesia and the risk of TTB, and the availability of FDA-licensed and approved 
devices.  FDA may modify these recommendations in the future based on scientific 
evidence as it becomes available, for example, if we determine that regional NAT testing 
alone does not adequately reduce the risk of TTB or if there is a need to expand the 
recommendations to include additional Babesia-risk states as they are identified.  In 
addition, we may modify the recommendations in the future based on the availability of 
licensed serology tests and approved pathogen reduction devices.   
 
  6  Contains Nonbinding Recommendations 
1.  We recommend that you update your donor history questionnaire, including 
full-length and abbreviated donor history questionnaires, and accompanying 
materials as necessary to incorporate the recommendations provided in this 
document.  You must update your standard operating procedures to reflect any 
such changes (21 CFR 606.100(b)). 
 
2.  To comply with the requirements in 21 CFR 610.40(a)(3), you must test 
donations as described in section V.A.3. of this document or implement 
pathogen reduction technology for platelets and plasma using an FDA-
approved pathogen reduction device effective against Babesia, according to 
the manufacturers instructions for use.  If an FDA-approved pathogen 
reduction device becomes available for Whole Blood or red blood cells that 
effectively inactivates Babesia, you may implement pathogen reduction 
technology for such blood components.    
 
3.  You must test each donation for evidence of Babesia using a licensed NAT3 
when collected in Connecticut, Delaware, Maine, Maryland, Massachusetts, 
Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode 
Island, Vermont, Virginia, Wisconsin and Washington, D.C. (21 CFR 
610.40(a)(3) and 610.40(b)).  Testing must be performed year-round and in 
accordance with the instructions for use of the device (21CFR 610.40 (a)(3) 
and 606.65(e)). 
 
a.  You must defer donors with a reactive NAT result for Babesia for at 
least 2 years from the date of the reactive donation (21 CFR 610.41(a) 
and 21 CFR 630.35(a)).  You must make reasonable attempts to notify 
any donor whose blood tests reactive for Babesia of their deferral and 
of their test results, within 8 weeks after determining that the donor is 
deferred (21 CFR 630.40).  Deferred donors must be counseled about 
the possible medical significance of the results (21 CFR 630.40(b)).  
 
b.  When testing or pathogen reduction is performed, you may discontinue 
asking donors questions about a history of babesiosis.4  If you choose 
                                                 
3 Blood establishments that are participating in a clinical trial and testing for Babesia using an unlicensed NAT may 
continue in the clinical trial but must implement the regulatory requirement to use a licensed donor screening test for 
Babesia nucleic acid by 12 months of this guidance issuance date (21 CFR 610.40(b)).  
4 To provide for appropriate donor screening and testing for this RTTI, the Director of the Center for Biologics 
Evaluation and Research is providing an alternative procedure (testing, as described in section V. of this document) 
under 21 CFR 640.120(b) to the provisions in 21 CFR 630.10 that require blood establishments to assess donors for 
risk factors for babesiosis before collecting blood or blood components.  Specifically, FDA is not recommending 
assessing donors for risk factors for babesiosis, in particular, travel to or residence in an area endemic or at risk for 
babesiosis.  Assessing donors for travel to or residence within the United States and deferring donors for time spent 
in areas endemic or at risk for babesiosis is not feasible because of the anticipated detrimental effect on the blood 
supply.  Approximately one-quarter of the U.S. population resides in the states identified at risk for babesiosis in this 
guidance, and a large number of prospective blood donors may travel to the at-risk states.   
  7  Contains Nonbinding Recommendations 
to ask a donor question about Babesia, you should follow the 
recommendations in section V.A.4. of this document.  
 
c.  When testing or pathogen reduction is performed, donors who were 
previously deferred for a history of babesiosis based on their responses 
on the donor history questionnaire may be eligible to donate provided 
they have not had a positive test result for Babesia in the last 2 years 
obtained from either a medical diagnosis or a positive donor screening 
test result and they meet all other donor eligibility criteria (21 CFR 
630.35(b)).   
 
4  In states that do not test donations for Babesia or pathogen reduce blood 
components we recommend the following:  
 
a.  Revise your donor history questionnaire to ask prospective donors if 
they have ever had a positive test result for Babesia, obtained from 
either a medical diagnosis or a reactive donor screening test.  
 
b.  You must defer donors who report a history of a positive test result for 
Babesia, obtained from either a medical diagnosis or a reactive donor 
screening test result (21 CFR 630.10(h)).  Such donors should be 
indefinitely deferred or deferred for at least 2 years from the date of 
the positive test and evaluated for requalification as described below in 
section V.A.4.c. of this document.    
 
c.  A donor who was previously deferred for a history of babesiosis or is 
deferred for a history of a positive test result for Babesia may be 
eligible to donate under 21 CFR 630.35(b) provided the following 
conditions are met: 
 
i.  On the day of donation, the donor has not had a positive test 
result for Babesia in the last 2 years and they meet all other 
eligibility criteria. 
 
ii.  The donation must be tested for Babesia by a licensed NAT 
and found to be nonreactive at the time of blood collection  
(21 CFR 610.40(a)(3)(ii)(A). 
 
If the donor meets the criteria for requalification in section 
V.A.4.c.i and ii., subsequent donations do not need to be tested 
for Babesia provided the donor is assessed by the DHQ and has 
not had a positive test for Babesia since the date of the last 
negative test result that was the basis for requalification.      
 
5.  For donor counseling purposes, the responsible physician may perform 
additional testing such as alternative Babesia NAT and/or diagnostic antibody 
  8  Contains Nonbinding Recommendations 
tests that are not indicated for use in donor screening.  The results of such 
testing cannot be used to requalify a deferred donor with a reactive screening 
test by a licensed NAT. 
 
B.  Product Management, Retrieval and Quarantine, Notification of Consignees 
of Blood and Blood Components  
 
1.  You may release donations that are nonreactive for Babesia by a licensed 
donor screening test provided all other donation suitability requirements are 
met (21 CFR 630.30). 
 
2.  You must not ship or use a donation that is reactive for Babesia, unless an 
exception for shipment or use is applicable (21 CFR 610.40(h) and 21 CFR 
630.30(b)(1)). 
 
3.  We recommend that you take the following actions when a donation tests 
reactive for Babesia by a licensed donor NAT:  
 
a.  Identify all cellular blood components previously collected from that 
donor in the 12 months prior to the date of the reactive index donation. 
The responsible physician may also consider the disposition of in-date 
cellular components (e.g., frozen RBC components) collected more 
than 12 months prior to the reactive index donation, especially those 
that were not tested; and 
 
b.  Quarantine the identified in-date cellular components held at your 
establishment; and    
 
c.  Notify consignees of all identified cellular blood components collected 
from the donor in the 12 months prior to the date of the reactive index 
donation that have been distributed, and: 
 
1.  Retrieve the identified in-date cellular blood components.  
2.  If components were transfused, encourage consignees to have a 
discussion with the recipients physician of record about a 
possible risk of TTB, particularly if the involved component(s) 
had not been tested or pathogen reduced. 
 
The recommendation for consignee notification and retrieval does not 
apply to previously distributed cellular blood components that were 
pathogen reduced using an FDA-approved device according to its 
instructions for use.    
 
4.  We recommend that you take the following actions when a donor later reports 
a history of a positive test result for Babesia and should have been deferred 
according to the recommendations in section V.A.4.b.  
  9  Contains Nonbinding Recommendations 
  
a.  Identify all cellular blood components previously collected from that 
donor going back 12 months prior to the reported date of the positive 
test result for Babesia; and 
  
b.  Quarantine the identified in-date cellular components held at your 
establishment; and 
 
c.  Notify consignees of all identified cellular blood components collected 
from the donor in the 12 months prior to the reported date of the 
positive test for Babesia and retrieve the identified in-date cellular 
blood components.  This recommendation does not apply to previously 
distributed cellular blood components that were pathogen reduced 
using an FDA-approved device according to its instructions for use.    
 
5.  If you previously collected acellular blood components (i.e., frozen plasma 
products) intended for transfusion or for further manufacturing from a donor 
that tests reactive for Babesia by a licensed donor NAT or from a donor who 
later reports a history of a positive test result for Babesia and should have 
been deferred according to the recommendations in section V.A.4.b, 
quarantine any in-date acellular blood components held at your establishment 
collected from the donor in the 12 months prior to the date of the reactive 
index donation or reported date of a positive test for Babesia.   
 
Note:  Based on the very low risk of TTB associated with frozen acellular blood 
components, we are not recommending notification of consignees or product 
retrieval if you distributed such products. 
 
C.  Product Disposition and Labeling 
 
1.  We recommend that you destroy or relabel blood and blood components that 
were collected from a donor who should have been deferred based on their 
responses to the DHQ according to the recommendations in section V.A.4. of 
this document.  If you relabel the blood and blood components, they may be 
released for research if labeled appropriately as described below.  
 
You must label the unit as required under 21 CFR 606.121.  You must use the 
following statements to prominently relabel the blood and blood components 
(21 CFR 606.121(c)):  
 
a.  NOT FOR TRANSFUSION:  Collected from a Donor with a History 
of a Positive Test Result for Babesia  
 
AND   
 
b.  Caution:  For Laboratory Research Only 
  10  Contains Nonbinding Recommendations 
 
2.  We recommend that you destroy or relabel blood and blood components 
that test reactive for Babesia by a licensed donor NAT.  If you relabel the 
blood and blood components, they may be released for research or for 
further manufacture into non-injectable products or in vitro diagnostic 
reagents when no other suitable sources are available, when written 
approval by FDA is obtained and if labeled appropriately as described 
below. (see 21 CFR 610.40(h)(2)(ii)) 
 
  You must label the reactive unit as required under 21 CFR 606.121 and 
with the BIOHAZARD legend (21 CFR 610.40(h)(2)(ii)(B)).  You must 
use the following statements to prominently relabel the blood components 
(21 CFR 606.121(c)): 
 
a.  NOT FOR TRANSFUSION:  Collected from a Donor Determined to 
be Reactive for Babesia   
 
AND 
 
b.  Caution:  For Laboratory Research Only  
 
OR  
 
Caution:  For Further Manufacturing into In Vitro Diagnostic Reagents 
for Which There Are No Alternative Sources  
 
OR 
 
Caution:  For Further Manufacturing Use as a Component of a Medical 
Device for Which There Are No Alternative Sources  
 
D.  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.   
 
1.  When testing is performed, you must update your circular of information (21 
CFR 606.122(h)).  We recommend the following statement: 
 
A licensed NAT for Babesia has been performed and found to be nonreactive.  
 
2.  If a blood system distributes components from both tested and untested 
donations, we recommend the following statement:  
 
A licensed NAT for Babesia has been performed and found to be nonreactive for 
blood collected in states where testing is required by FDA.    
  11  Contains Nonbinding Recommendations 
 
 
VI.  IMPLEMENTATION AND REPORTING CHANGES UNDER 21 CFR 601.12 
 
You may implement the recommendations as soon as feasible. FDA intends to begin requiring 
compliance with the underlying regulatory requirements regarding relevant transfusion-
transmitted infection screening, testing, and product management 12 months after the guidance 
issuance date.  Licensed blood establishments must report changes under 21 CFR 601.12, as 
follows:   
 
A.  Donor History Questionnaire 
 
Licensed blood establishments that modify the donor history questionnaire (DHQ) must 
report the change under 21 CFR 601.12 as follows:  
 
1.  If you implement testing of each donation for Babesia or pathogen reduction 
consistent with the recommendations in section V.A.3. of this document, you 
may remove the current question regarding a history of babesiosis from your 
DHQ.  Report this change in your next annual report, noting the date the 
change was made (21 CFR 601.12(d)). 
 
2.  If you do not implement testing for Babesia or pathogen reduction, you should 
revise your current DHQ consistent with the recommendations in section 
V.A.4. of this document.  Revising the existing question on babesiosis or 
using a revised DHQ found acceptable to FDA is considered a minor change 
and must be reported in your next annual report, noting the date that the 
change was made (21 CFR 601.12(d)). 
 
3.  You must submit a Prior Approval Supplement if you wish to revise your 
DHQ other than as recommended in section V.A.4. of this document, as this 
constitutes a major change (21 CFR 601.12(b)(1)).  
 
B.  Testing 
 
Licensed blood establishments that implement testing for Babesia must report the change 
under 21 CFR 601.12 as follows: 
 
1.  If you implement testing consistent with the recommendations in section 
V.A.3. of this document, submit the change in an annual report under 21 CFR 
601.12 (d),5 noting the date that the testing was implemented.    
 
2.  You must submit a Prior Approval Supplement if you wish to implement a 
testing strategy other than as recommended in section V.A.3. of this document 
(21 CFR 601.12(b)(1)).  
                                                 
5 See 21 CFR 601.12 (a)(3). 
  12  Contains Nonbinding Recommendations 
 
Note:  If you wish to implement a testing strategy that is more restrictive (e.g., 
testing in other states in addition to those required or nationwide testing) than 
recommended in this document, you may submit the change as an annual report 
under 21 CFR 601.12. 
 
C.  Circular of Information 
 
Licensed blood establishments that update their circular of information to include a test 
statement recommended in this document must report this change under 21 CFR 601.12. 
You may include this change in your supplement reporting implementation of testing or 
you may include it in your next annual report. 
 
 
 
 
 
  13  Contains Nonbinding Recommendations 
 
VII.  REFERENCES 
 
1.  Jacoby, G.A., et al., Treatment of transfusion-transmitted babesiosis by exchange 
transfusion. N Engl J Med, 1980. 303(19):1098-1100. 
2.  Herwaldt, B.L., et al., Transfusion-associated babesiosis in the United States: a description 
of cases. Ann Intern Med, 2011. 155(8):509-519. 
3.  Brennan, M.B., et al., Transmission of Babesia microti Parasites by Solid Organ 
Transplantation. Emerg Infect Dis, 2016. 22(11):1869-1876. 
4.  Western, K.A., et al., Babesiosis in a Massachusetts resident. N Engl J Med, 1970. 
283(16):854-856. 
5.  Vannier, E. and P.J. Krause, Human babesiosis. N Engl J Med, 2012. 366(25): 2397-2407. 
6.  Persing, D.H., et al., Infection with a babesia-like organism in northern California. N Engl J 
Med, 1995. 332(5):298-303. 
7.  Conrad, P.A., et al., Description of Babesia duncani n.sp. (Apicomplexa: Babesiidae) from 
humans and its differentiation from other piroplasms. Int J Parasitol, 2006. 36(7):779-789. 
8.  Herwaldt, B.L., et al., Babesia divergens-like infection, Washington State. Emerg Infect Dis, 
2004. 10(4):622-629. 
9.  Krause, P.J., et al., Increasing health burden of human babesiosis in endemic sites. Am J 
Trop Med Hyg, 2003. 68(4):431-436. 
10. Moritz, E.D., et al., Screening for Babesia microti in the U.S. Blood Supply. N Engl J Med, 
2016. 375(23):2236-2245. 
11. Krause, P.J., et al., Persistent parasitemia after acute babesiosis. N Engl J Med, 1998. 
339(3):160-165. 
12. MMWR Summary of Notifiable DiseasesUnited States, 2011. Centers for Disease Control 
and Prevention, 60 (53):1-117. July 5, 2013. 
13. MMWR Summary of Notifiable DiseasesUnited States, 2012. Centers for Disease Control 
and Prevention, 61(53):1-121. September 19, 2014. 
14. MMWR Summary of Notifiable Infectious Diseases and ConditionsUnited States, 2013. 
Centers for Disease Control and Prevention, 62(53). October 23, 2015. 
15. MMWR Summary of Notifiable Infectious Diseases and ConditionsUnited States, 2014. 
Centers for Disease Control and Prevention, 63(54);1-23. October 14, 2016. 
16. MMWR Notifiable Diseases and Mortality Tables. Centers for Disease Control and 
Prevention, 66 (52). January 5, 2018.   
17. MMWR Summary of Notifiable Infectious Diseases and ConditionsUnited States, 2015. 
Centers for Disease Control and Prevention, 64(53);1-143. August 11, 2017. 
18. Reubush, T.K., et al., Human babesiosis on Nantucket Island.  Evidence for Self-Limited and 
Subclinical Infections. N Engl J Med, 1977. 297(15):825-827. 
19. White, D.J., et al., Human babesiosis in New York State: Review of 139 hospitalized cases 
and analysis of prognostic factors. Arch Intern Med, 1998. 158(19):2149-2154. 
20. Hatcher, J.C., et al., Severe babesiosis in Long Island:  Review of 34 cases and their 
complications. Clin Infect Dis, 2001. 32(8):1117-1125. 
21. Levin, A.E., et. al., Transfusion-transmitted babesios: Is it time to screen the blood supply? 
Curr Opin Hematol. 2016 November; 23(6):573-580. 
22. Linden, J.V., et al., Transfusion-transmitted and community-acquired babesiosis in New 
York, 2004 to 2015. Transfusion, 2018. 660-668. 
23. Burgess, M.J., et al., Possible Transfusion-Transmitted Babesia divergens-like/MO-1 
Infection in an Arkansas Patient. Clin Infect Dis, 2017. 64(11):1622-1625. 
14  Contains Nonbinding Recommendations 
24. Tonnetti, L., et al., Transfusion-transmitted Babesia microti identified through 
hemovigilance. Transfusion, 2009. 49(12):2557-2563. 
25. Blood Products Advisory Committee Meeting. FDA. May 13, 2015. http://wayback.archive-
it.org/7993/20170722221132/https://www.fda.gov/AdvisoryCommittees/CommitteesMeeting
Materials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm441228.
htm. 
26. Menis, M., et al., Babesiosis Occurrence among the Elderly in the United States, as 
Recorded in Large Medicare Databases during 2006-2013. PLoS One, 2015. 
10(10):e0140332. 
27. Biological Product Deviation Reports Annual Summaries. FDA. 
https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/Biological
ProductDeviations/ucm129757.htm.  
28. Approaches to Reduce Risk of Transfusion-Transmitted Babesiosis in the United States, 
Public Workshop. (July 11, 2008, 73 FR 39972). 
29. Gubernot, D.M., et al., Transfusion-transmitted babesiosis in the United States: Summary of 
a workshop. Transfusion, 2009. 49(12):2759-2771. 
30. Blood Products Advisory Committee Meeting. FDA. July 26, 2010. https://wayback.archive-
it.org/7993/20170111180050/http://www.fda.gov/AdvisoryCommittees/CommitteesMeeting
Materials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm205013.
htm. 
31. Kumar, S., Risk of Babesia Infection by Blood Transfusion and Potential Strategies for 
Donor Testing:  Introduction. BPAC meeting July 26, 2010. 
32. Herwaldt, B., Epidemiology of Babesiosis, including Transfusion-Associated Infection 
BPAC:  Risk of Babesia Infection by Blood Transfusion and Potential Strategies for Donor 
Testing. July 26, 2010. 
33. Leiby, D., Experience with Testing Blood Donors for Babesia. BPAC:  Risk of Babesia 
Infection by Blood Transfusion and Potential Strategies for Donor Testing. July 26, 2010. 
34. Walderhaug, M., et al., Transfusion Transmitted Babesiosis Risk Assessment. BPAC:  Risk 
of Babesia Infection by Blood Transfusion and Potential Strategies for Donor Testing. July 
26, 2010. 
35. Stramer, S., Investigational Blood Donor Screening for Babesia microti:  Implications For 
Blood Safety. BPAC:  Strategies for Implementation of Serological and Nucleic Acid Testing 
for Babesia microti in Blood Donors. May 13, 2015. 
36. Levin, A.E., Screening with an investigational enzyme immunoassay for Babesia microti 
evaluated in an  IND study on U.S. blood donor populations. BPAC:  Strategies for 
Implementation of Serological and Nucleic Acid Testing for Babesia microti in Blood 
Donors. May 13, 2015. 
 
 
 
  
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