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

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

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

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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

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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).

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This guidance consolidates FDA’s 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.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.
The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.
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

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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 donor’s 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.

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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.

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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):

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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 donor’s 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.

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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 donor’s 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.

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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

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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)).

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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.
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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

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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.
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12. O’Brien 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.
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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 T‐lymphotropic 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

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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

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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.