Use of Serological Tests to Reduce the 
Risk of Transfusion-Transmitted 
Human T-Lymphotropic Virus Types 
I and II (HTLV-I/II) 
 
 
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/vaccines-blood-biologics/guidance-compliance-
regulatory-information-biologics/biologics-guidances 
 
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 
February 2020  Contains Nonbinding Recommendations 
 
Table of Contents 
 
I.  INTRODUCTION............................................................................................................. 1 
 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS .................................................................................................. 4 
A.  Blood Donation Testing, Donor Deferral and Notification ............................... 4 
1.  Donation Testing ............................................................................................... 4 
2.  Donor Deferral and Notification ....................................................................... 4 
B.  Requalification of Blood Donors Deferred Because of Reactive Test Results 
for Anti-HTLV-I/II ............................................................................................... 5 
C.  Product Management ........................................................................................... 7 
1.  Index Donations ................................................................................................ 7 
2.  Product Retrieval, Quarantine and Consignee Notification .............................. 7 
3.  Disposition of Prior Collections from Donors with Reactive Screening Tests 
Placed in Quarantine ......................................................................................... 8 
IV.  IMPLEMENTATION ...................................................................................................... 8 
V.  REFERENCES ................................................................................................................ 10 
APPENDIX .................................................................................................................................. 13 
 
i  Contains Nonbinding Recommendations 
 
Use of Serological Tests to Reduce the Risk of Transfusion-
Transmitted Human T-Lymphotropic Virus Types I and II  
(HTLV-I/II) 
 
 
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 human T-lymphotropic virus type 
I (HTLV-I) and type II (HTLV-II), collectively referred to as HTLV-I/II, by blood and blood 
components.  These recommendations apply to the collection of Whole blood and blood 
components, except Source Plasma. 
 
HTLV-I/II is a relevant transfusion-transmitted infection (RTTI) (Title 21 of the Code of Federal 
Regulations (CFR) 630.3(h)(1)(iv)) and, therefore, subject to the testing requirements in 21 CFR 
610.40, the donor deferral requirements in 21 CFR 610.41, and the donor notification 
requirements in 21 CFR 630.40.  Blood establishments are not required to test Source Plasma for 
HTLV-I/II (21 CFR 610.40(a)(2)(ii)).  Therefore, this guidance does not apply to the collection 
of Source Plasma.  
 
FDA previously issued recommendations on HTLV-I/II in the following documents to blood 
establishments: 
  HTLV-I Antibody Testing, Memorandum, November 29, 1988 (November 1988 
memorandum).  
  HTLV-I Antibody Testing, Memorandum, July 6, 1989 (July 1989 memorandum). 
  Recommendations for the Quarantine and Disposition of Units from Prior Collections 
from Donors with Repeatedly Reactive Screening Tests for Hepatitis B Virus (HBV), 
Hepatitis C Virus (HCV) and Human T- Lymphotropic Virus Type I (HTLV-I), 
Memorandum, July 19, 1996 (July 1996 memorandum).  
  Guidance for Industry:  Donor Screening for Antibodies to HTLV-II; August 1997 
(August 1997 guidance). 
  Recommendations for Requalification of Blood Donors Deferred Because of Reactive 
Test Results for Antibodies to Human T-Lymphotropic Virus Types I and II (anti-HTLV-
I/II); Draft Guidance for Industry, September 2018 (September 2018 draft guidance).  
 
1  Contains Nonbinding Recommendations 
 
This guidance consolidates FDAs current recommendations on HTLV-I/II, as follows: 
  Finalizes the September 2018 draft guidance.  
  Supersedes the recommendations specific to HTLV-I contained in the July 1996 
memorandum. 
  Supersedes the November 1988 and July 1989 memoranda, and the August 1997 
guidance. 
 
The only new recommendations contained in this guidance are those related to donor 
requalification found in section III.B.  All other recommendations reflect current regulations and 
the availability of a licensed supplemental test for antibodies to HTLV-I/II (anti-HTLV-I/II) and 
are otherwise consistent with our previously issued recommendations.  
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the 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 
 
Human T-lymphotropic virus types I and II (HTLV-I/II) are retroviruses that may cause severe 
hematological and neurological diseases in infected individuals (Ref. 1).  The HTLV family 
consists of genetically- and immunologically-related members, including HTLV-I and HTLV-II 
(Ref. 1).  HTLV-I is associated with adult T-cell leukemia/lymphoma (ATL) (Refs. 2-3), HTLV-
Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (Ref. 4) and HTLV-associated 
uveitis (Ref. 5).  HTLV-II is associated with hairy cell leukemia although its role in disease 
development has not been established (Ref. 6).   
 
HTLV-I is highly prevalent in Japan, Central Africa, Caribbean Islands, North, Central and 
South America, the Melanesian Islands in the Pacific and in the aboriginal population in 
Australia.  HTLV-II infection has been documented in African populations and in Native 
Americans in North, Central and South America (Refs. 7-8).  HTLV transmission is lymphocyte 
mediated and requires cell-to-cell contact (Ref. 9).  The viruses can be transmitted from mother 
to child via breast-feeding, by sexual exposure and blood transfusion.  Recent epidemiological 
studies in the United States (U.S.) and Europe confirm the presence of both HTLV-I and HTLV-
II among high-risk populations such as illicit injection drug users (IDU) (Refs. 10-15).  
 
Before licensed blood donation screening tests for HTLV were available, a prospective study in 
an endemic population showed a 44% seroconversion rate in recipients of HTLV-I positive 
cellular components (Ref. 16).  HTLV is a cell-associated virus hence viral transmission has not 
been observed with acellular (plasma) components.  Cases of transfusion-transmission are rare, 
and none were found by recipient tracing (lookback) in the American Red Cross, likely reflecting 
the relatively low probability of transmission and short viremic window period (Ref. 17).  
Retrospective studies for transfusion transmission are further complicated by the difficulty in 
recognizing cases because HTLV infection is typically asymptomatic for decades.  In one report 
2  Contains Nonbinding Recommendations 
 
of transfusion-transmitted HTLV, however, a U.S. Army soldier tested positive for HTLV-I 44 
days after receiving emergency (untested) fresh whole blood transfusions.  The investigation 
implicated one of the transfused components because the donor had confirmed-positive anti-
HTLV-I results based on retrospective testing and genetic analysis of HTLV-I sequences 
demonstrated linkage of the viruses isolated from the donor and the recipient (Ref. 18). 
 
FDA has recommended blood donation screening for antibodies to HTLV-I since 1988 and to 
HTLV-II since 1998.  The licensed donor screening assays detect antibodies against both HTLV 
I and II in blood donations.1  Consistent with 21 CFR 610.40(h), donations that test reactive on 
the licensed screening tests must not be used for transfusion.  However, donors who test reactive 
for anti-HTLV I/II on only one occasion are not deferred unless further testing is positive (see 21 
CFR 610.41(a)(1)).  
 
Before the availability of a licensed supplemental test to confirm infection in a donor with 
repeatedly reactive anti-HTLV-I/II screening results, blood centers typically performed further 
testing with a second (different) licensed blood donation screening test on the same donation or a 
subsequent donation.  Donors who tested reactive on more than one occasion or tested reactive 
with two different tests on the same donation were deferred.  Historically, additional testing 
could have also included an investigational test, or research-only confirmatory algorithms, 
utilizing a combination of enzyme-linked immunosorbent assay (ELISA), immunofluorescence 
assays (IFA), western blot, and/or radioimmunoprecipitation assays (RIPA) in a defined 
sequence (e.g., California Department of Public Health Laboratory HTLV supplemental 
algorithm) (Refs. 14, 19-20).  
 
The Blood Products Advisory Committee discussed the interpretive criteria for use of an 
investigational HTLV-I/II supplemental western blot test in 2013 (Ref. 21).  FDA licensed the 
western blot supplemental test for anti-HTLV-I/II in 2014 (Ref. 22).  Further testing of each 
donation found to be reactive for anti-HTLV I/II using a licensed, approved, or cleared 
supplemental test is required under 21 CFR 610.40(e) to provide additional information 
concerning the reactive donors infection status.  
 
About 5% of donations with repeatedly-reactive screening test results are confirmed positive 
based on further testing (Ref. 11).  In a recent U.S. surveillance study comprising more than 14 
million blood donations, the confirmed-positive HTLV I/II rate was 0.34 per 10,000 donations 
(Ref. 23).  Between 1995 and 2009, the American Red Cross reported that more than 70,000 
donors with unconfirmed HTLV screening test results potentially could be requalified for 
donation (Ref. 11).  In this guidance, FDA is providing recommendations for a requalification 
method under 21 CFR 610.41(b) to reenter donors deferred because of anti-HTLV-I/II screening 
tests results. 
 
In the regulations, we refer to screening tests as reactive to accommodate the different testing 
algorithms.  In this guidance, the term reactive, which is used interchangeably with repeatedly 
                                                 
1 A list of tests licensed for use in blood donor screening and supplemental testing is available on the FDA website, 
at https://www.fda.gov/vaccines-blood-biologics/blood-donor-screening/complete-list-donor-screening-assays-
infectious-agents-and-hiv-diagnostic-assays. 
 
3  Contains Nonbinding Recommendations 
 
reactive, or the term nonreactive is used to describe the screening test results for anti-HTLV 
on a donation.  In addition, the terms positive, indeterminate and negative are used to refer 
to the final interpretation of supplemental test results. 
 
 
III.  RECOMMENDATIONS 
 
These recommendations apply to the collection of Whole Blood and blood components for 
transfusion or for further manufacturing, except Source Plasma.  
 
A.  Blood Donation Testing, Donor Deferral and Notification  
 
1.  Donation Testing  
 
You must test each donation for evidence of HTLV-I/II infection (21 CFR 
610.40(a)(2)) using a licensed screening test for anti-HTLV-I/II (21 CFR 610.40(b)), 
subject to the exceptions found in 21 CFR 610.40 (c) and (d).   
 
You must not ship or use blood or blood components that test reactive for anti-
HTLV-I/II unless an exception exists (21 CFR 610.40(h)(2) and 21 CFR 
630.30(b)(1)).  
 
You must further test each donation found reactive on a licensed screening test for 
anti-HTLV-I/II with a licensed, approved, or cleared supplemental test for HTLV-I/II 
(21 CFR 610.40(e)).  
 
2.  Donor Deferral and Notification 
 
You are not required to defer a donor who tests reactive for anti-HTLV-I/II on only 
one occasion. (21 CFR 610.41(a)(1)).  However, you must defer the donor if: 
  the donor is found to be positive upon further testing for HTLV under 21 CFR 
610.40(e); or  
  a second, licensed cleared or approved screening test for HTLV has been 
performed on the same donation under 21 CFR 610.40(a) and is reactive; or  
  the donor tests reactive for anti-HTLV-I/II on more than one occasion. 
 
Further, under 21 CFR 630.40, you must make reasonable attempts to notify any 
donor that has been deferred based on the results of testing for anti- HTLV-I/II.  You 
must attempt to obtain the results of further testing required under 21 CFR 610.40(e) 
prior to notifying a donor of the deferral.  You must notify the donor that they are 
deferred and of the test results that were the basis for the deferral, including the 
results of further testing.  When appropriate, you must provide information 
concerning medical follow up and counseling.  You must make reasonable attempts 
to notify the donor within 8 weeks after determining that the donor is deferred.   
 
4  Contains Nonbinding Recommendations 
 
A deferred donor subsequently may be found to be eligible by a requalification 
method or process found acceptable for such purposes by FDA. (21 CFR 610.41(b)).  
See recommendations for a donor requalification method in section III. B of this 
guidance.  
 
B.  Requalification of Blood Donors Deferred Because of Reactive Test Results 
for Anti-HTLV-I/II 
 
We consider the recommendations in this section to be an acceptable requalification 
method, within the meaning of 21 CFR 610.41(b), for reentry of donors deferred because 
of reactive screening test results for anti-HTLV-I/II under 21 CFR 610.41(a)(1).  
 
1.  We recommend that individuals who were indefinitely deferred with the 
following test results at any time are not eligible for reentry: 
 
a.  Positive for anti-HTLV-I/II with an investigational or licensed 
supplemental test  
 
OR  
 
b.  Positive final interpretation with a research-use supplemental HTLV 
algorithm (e.g., California Department of Public Health Laboratory HTLV 
algorithm). 
 
2.  We recommend that donors who have been indefinitely deferred may be 
considered for reentry if they had the following test results at the time of the 
donation that prompted the deferral: 
 
a.  Negative or indeterminate for anti-HTLV-I/II with an investigational test 
or licensed supplemental test  
 
OR  
 
b.  Negative or indeterminate final interpretation with a research-use 
supplemental HTLV algorithm (e.g., California Department of Public 
Health Laboratory HTLV algorithm) before the licensed supplemental test 
was available  
 
OR 
 
c.  Not further tested for anti-HTLV-I/II before the licensed supplemental test 
was available. 
 
3.  To reenter a donor who meets the criteria described in section III.B.2 of this 
guidance, we recommend the following actions (also see Appendix of this 
guidance): 
5  Contains Nonbinding Recommendations 
 
 
a.  At least 6 months after the date of deferral, collect a new blood sample 
from the donor (no donation is made at this time). 
 
b.  Test the sample with two different licensed screening tests for  
anti-HTLV-I/II.  One of the two screening tests should be the test that was 
repeatedly reactive on the donation that resulted in deferral if the test is 
still available. 
 
c.  Evaluate the results of the follow-up testing of the donors new sample as 
follows: 
 
i.  If both screening tests are nonreactive (negative for anti-HTLV-
I/II), you may reenter the donor, provided all other donor eligibility 
criteria are met at the time of donation. 
 
ii.  If both screening tests are repeatedly reactive, you must defer the 
donor permanently. 
 
iii.  If one screening test is repeatedly reactive and one is nonreactive, 
the donor remains deferred, but you may perform a licensed 
supplemental test. 
 
  If the licensed supplemental test is positive or 
indeterminate, you must defer the donor permanently. 
 
  If the licensed supplemental test is negative, you may re-
test the donor for reentry after one more waiting period of 
at least 6 months (see section III.B.3.a of this guidance). 
 
- If both screening tests are nonreactive, you may 
reenter the donor, provided all donor eligibility criteria 
are met.  
 
- If one or both screening tests are repeatedly reactive 
on the follow-up sample, you must defer the donor 
permanently. 
 
If a deferred donor is tested for anti-HTLV-I/II before the end of the 6-month waiting 
period, the results may be used for donor notification purposes or for counseling.  
However, only nonreactive results obtained at least 6 months after the last reactive 
donation for anti-HTLV-I/II may be used for reentry purposes.  If either one or both 
screening tests are repeatedly reactive at any time, you must defer the donor permanently. 
   
6  Contains Nonbinding Recommendations 
 
C.  Product Management 
 
1.  Index Donations 
 
You must not ship or use blood and blood components that test reactive for anti- 
HTLV-I/II 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 unsuitable (21 CFR 606.121(f)).  We recommend the following 
statement:  
 
Reactive by a test for HTLV-I or HTLV-II antibodies. The risk of transmission 
of HTLV-I or HTLV-II is present. 
 
In addition, when an exception under 21 CFR 610.40(h) exists, blood and blood 
components that test reactive for anti-HTLV-I/II should also be labeled with one of 
the following additional statements: 
 
Caution:  For further manufacture into in vitro diagnostic reagents for which 
there are no alternative sources or  
 
Caution:  For laboratory research use only. 
 
2.  Product Retrieval, Quarantine and Consignee Notification 
 
Within 1 week of a reactive HTLV-I/II screening test result that results in deferral, 
you should: 
 
a.  Identify all in-date Whole Blood collections and cellular blood 
components previously donated by the donor, going back either 5 years or, 
in a previously tested donor, 12 months prior to the donors most recent 
nonreactive test result with a licensed test for anti-HTLV-I/II, whichever 
is the lesser period (the lookback period).  
 
b.  Quarantine all identified Whole Blood collections and cellular blood 
components from that donor held at your establishment; and 
 
c.  Notify consignees to quarantine all previously distributed, identified 
Whole Blood and cellular components.  
 
We are not recommending quarantine for acellular blood components (i.e., frozen plasma 
components) from prior collections from donors who subsequently test repeatedly 
reactive for anti-HTLV-I/II because of the very low risk of transfusion-transmitted HTLV 
associated with such components. 
7  Contains Nonbinding Recommendations 
 
 
3.  Disposition of Prior Collections from Donors with Reactive Screening Tests 
Placed in Quarantine 
 
Prior collections from donors with reactive screening tests that were placed in 
quarantine may be released for transfusion or further manufacture if the donor's 
current sample is further tested by a licensed, approved or cleared supplemental test 
for HTLV under 21 CFR 610.40(e) and the donor is found to be negative.  
 
If further testing is not performed within 30 days or the donor tests positive or 
indeterminate on the supplemental test, then the quarantined units should be 
destroyed or relabeled consistent with the recommendations in section III.C.1 of this 
guidance.   
 
 
IV.  IMPLEMENTATION  
 
We recommend that you report implementation of the new recommendations in this guidance 
(i.e., the recommendations in section III. B of this guidance with respect to donor requalification) 
as follows:   
 
A.  For blood establishments that implement the recommendations for requalification in 
this guidance without modification and in their entirety: 
 
1.  We consider the implementation of the recommendations for requalification in 
this guidance without modification and in their entirety to be a minor change, 
because FDA has determined that implementation in this manner has a minimal 
potential to have an adverse effect on the identity, strength, quality, purity, or 
potency of the product as they may relate to the safety or effectiveness of the 
product.  Licensed blood establishments must report this change to FDA in their 
annual report under 21 CFR 601.12(d), noting the date the method was 
implemented. 
 
2.  Unlicensed blood establishments are not required to report this change to FDA. 
 
B.  For blood establishments that wish to implement an alternative requalification method 
for donors deferred for reactive anti-HTLV I/II: 
 
1.  We consider the implementation of an alternative requalification method to be a 
major change with a substantial potential to have an adverse effect on the identity, 
strength, quality, purity, or potency of the product as they may relate to the safety 
or effectiveness of the product.  Therefore, licensed blood establishments must 
8  Contains Nonbinding Recommendations 
 
submit a Prior Approval Supplement (PAS) to FDA under 21 CFR 601.12(b).  
The supplement should include the following: 
 
a. Form FDA 356h, Application to Market a New or Abbreviated New 
Drug or Biologic for Human Use, which may be obtained at  
https://www.fda.gov/about-fda/reports-manuals-forms/forms 
 
b. A cover letter, describing the request and the contents of the 
submission. 
 
c. A written SOP, describing the requalification method or process. 
 
2.  Similarly, before an unlicensed blood establishment implements an alternative 
requalification method, FDA must first find it acceptable (21 CFR 610.41(b)). 
   
9  Contains Nonbinding Recommendations 
 
V.  REFERENCES  
 
1.  Lairmore MD and Franchini G. Human T- cell leukemia virus type 1 and 2. Fields Virology 
Eds: Knipe DM and Howley PM. Lippincott, Williams & Wilkins Pub. 2007: 2071-2105.  
 
2.  Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, and Gallo RC. Detection and 
isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with 
cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 1980; 77(12): 7415-7419. 
https://www.ncbi.nlm.nih.gov/pubmed/6261256 
 
3.  Murphy EL, Hanchard B, Figueroa JP, Gibbs WN, Lofters WS, Campbell M, Goedert JJ and 
Blattner WA.  Modelling the risk of adult T-cell Leukemia/Lymphoma in persons infected 
with human T-Lymphotropic virus type I. Int. J. Cancer 1989; 43(2): 250-253. 
https://www.ncbi.nlm.nih.gov/pubmed/2917802  
 
4.  Kaplan JE, Osame M, Kubota H, Igata A, Nishitani H, Maeda Y, Khabbaz RF, and Janssen 
RS.  The risk of development of HTLV-I-associated Myelopathy/ Tropical Spastic 
Paraparesis among persons infected with HTLV-I. J. Acquir Immune Defic. Syndr. 1990; 
3(11): 1096-1101.  
https://www.ncbi.nlm.nih.gov/pubmed/2213510 
 
5.  Proietti FA, Carneiro-Proietti AB, Catalan-Soares BC, and Murphy EL.  Global 
epidemiology of HTLV-I infection and associated diseases.  Oncogene. 2005; 24(39): 6058-
6068. https://www.ncbi.nlm.nih.gov/pubmed/16155612 
 
6.  Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I, Blayney D, Golde D, 
and Gallo RC. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a 
T-cell variant of hairy cell leukemia. Science 1982; 218(4572): 571-573. 
https://www.ncbi.nlm.nih.gov/pubmed/6981847 
 
7.  Maloney EM, Biggar RJ, Neel JV, Taylor ME, Hahn BH, Shaw GM and Blattner WA.  
Endemic human T cell lymphotropic virus type II infection among isolated Brazilian 
Amerindians. J. Infec. Dis. 1992; 166(1): 100-107. 
https://www.ncbi.nlm.nih.gov/pubmed/1607683 
 
8.  Lowis GW, Sheremata WA and Minagar A.  Epidemiologic features of HTLV-II: serologic 
and molecular evidence. Ann. Epidemiol. 2002; 12(1): 46-66. 
https://www.ncbi.nlm.nih.gov/pubmed/11750240 
 
9.  Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber JN, Griffiths GM, Tanaka Y, 
Osame M, and Bangham CR. Spread of HTLV-I between lymphocytes by virus-induced 
polarization of the cytoskeleton. Science. 2003; 299(5613): 1713-1716. 
https://www.ncbi.nlm.nih.gov/pubmed/12589003 
 
10  Contains Nonbinding Recommendations 
 
10. Davison KL, Dow B, Barbara JA, Hewitt PE and Eglin R. The introduction of anti-HTLV 
testing of blood donations and the risk of transfusion-transmitted HTLV, UK: 2002-2006. 
Transfus. Med. 2009; 19(1): 24-34.  
https://www.ncbi.nlm.nih.gov/pubmed/19302452 
 
11. Zou S, Stramer SL and Dodd RY. Donor testing and risk: current prevalence, incidence and 
residual risk of transfusion-transmissible agents in US allogeneic donations. Transfus. Med. 
Rev. 2012; 26(2): 119-128. 
https://www.ncbi.nlm.nih.gov/pubmed/21871776 
 
12. OBrien SF, Goldman M, Scalia V, Yi QL, Fan W, Xi G, Dines IR and Fearon MA. The 
epidemiology of human T-cell lymphotropic virus types I and II in Canadian blood donors. 
Transfus. Med.  2013; 23(5): 358-366.  
https://www.ncbi.nlm.nih.gov/pubmed/23859527 
 
13. Martin JD, Mathias RG, Sarin C, and Byrne SE. Human T-lymphotropic virus type I and II 
infections in First Nations alcohol and drug treatment centres in British Columbia, Canada, 
1992-2000. Int. J. Circumpolar Health. 2002; 61(2): 98-103. 
https://www.ncbi.nlm.nih.gov/pubmed/12078968 
 
14. Stramer SL, Notari EP, Zou S, Krysztof DE, Brodsky JP, Tegtmeier GE and Dodd RY. 
Human T-lymphotropic virus antibody screening of blood donors: rates of false-positive 
results and evaluation of a potential donor reentry algorithm.  Transfus.  2011; 51(4): 692-
701. https://www.ncbi.nlm.nih.gov/pubmed/20946198 
 
15. Hewitt PE, Davison K, Howell DR and Taylor GP. Human T-lymphotropic virus lookback in 
NHS Blood and Transplant (England) reveals the efficacy of leukoreduction. Transfus. 2013; 
53(10): 2168-2175.  
https://www.ncbi.nlm.nih.gov/pubmed/23384161 
 
16. Manns A, Wilks RJ, Murphy EL, Haynes G, Figueroa JP, Barnett M, Hanchard B and 
Blattner WA. A prospective study of transmission by transfusion of HTLV-I and risk factors 
associated with seroconversion. Int. J. Cancer. 1992: 51(6): 886-891. 
https://www.ncbi.nlm.nih.gov/pubmed/1639536 
 
17. Stramer SL, Foster GA, Dodd RY. Effectiveness of human T-lymphotropic virus (HTLV) 
recipient tracing (lookback) and the current HTLV-I and -II confirmatory algorithm, 1999 to 
2004.  Transfus. 2006;46: 703-707.    
https://www.ncbi.nlm.nih.gov/pubmed/16686837 
 
18. Hakre S, Manak MM, Murray CK, Davis KW, Bose M, Harding AJ, Maas PR, Jagodzinski 
LL, Kim JH, Michael NL, Rentas FJ, Peel SA, Scott PT, and Tovanabutra S. Transfusion
transmitted human Tlymphotropic virus Type I infection in a United States military 
emergency whole blood transfusion recipient in Afghanistan, 2010. Transfus.  2013; 53(1): 
2176-2182. 
https://www.ncbi.nlm.nih.gov/pubmed/23362944 
11  Contains Nonbinding Recommendations 
 
 
19. Busch MP, Laycock M, Kleinman SH, Wages JW Jr, Calabro M, Kaplan JE, Khabbaz RF, 
Hollingsworth CG.  Accuracy of supplementary serologic testing for human T-lymphotropic 
virus types I and II in US blood donors.  Retrovirus Epidemiology Donor Study.  Blood 
1994;83(4): 1143-1148.  https://www.ncbi.nlm.nih.gov/pubmed/8111054 
 
20. Guidelines for counseling persons infected with human T-lymphotropic virus type I (HTLV-
I) and type II (HTLV-II). Centers for Disease Control and Prevention and the U.S.P.H.S. 
Working Group. Ann Intern Med 1993;118(6): 448-454. 
https://www.ncbi.nlm.nih.gov/pubmed/8382459. 
 
21. CBER FDA, 108th Meeting of the Blood Products Advisory Committee, Interpretive Criteria 
for the MP Diagnostics HTLV Blot 2.4, November 1, 2013. https://wayback.archive-
it.org/7993/20170113014636/http://www.fda.gov/downloads/AdvisoryCommittees/Committ
eesMeetingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/
UCM376955.pdf 
 
22. Package Insert: MP Diagnostics HTLV Blot 2.4 Western Blot Assay, December 2014. 
https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/Licen
sedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm426585.htm 
 
23. Dodd RY, Notari EP, Nelson D, Foster GA, Krysztof DE, Kaidarova Z, Milan-Benson L, 
Kessler DA, Shaz BH, Vahidnia F, Custer B, Stramer SL.  Development of a multisystem 
surveillance database for transfusion-transmitted infections among blood donors in the 
United States.  Transfus.  2016;56(11): 2781-2789. 
https://www.ncbi.nlm.nih.gov/pubmed/27557553 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12  Contains Nonbinding Recommendations 
 
APPENDIX 
 
Requalification Method for Blood Donors Deferred Because of  
Reactive Test Results for Anti-HTLV-I/II 
 
 
 
 
Abbreviations: NR, nonreactive (negative for anti-HTLV-I/II); RR, repeatedly reactive; positive 
(seropositive); negative (seronegative) 
 
1You may re-test the donor for reentry after one more waiting period of at least 6 months, using two different 
licensed anti-HTLV-I/II screening tests.  If both screening tests are negative, you may reenter the donor.  If either 
one or both screening tests are repeatedly reactive at any time, we recommend that you defer the donor permanently.  
 
 
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