Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria: Guidance for Industry

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

Contains Nonbinding Recommendations
Recommendations to Reduce the Risk
of Transfusion-Transmitted Malaria
_______________________________
Guidance for Industry
This guidance is for immediate implementation.
This guidance is being implemented in accordance with 21 CFR 10.115(g)(2) without prior
public comment because the Food and Drug Administration has determined that prior public
participation for this guidance is not feasible or appropriate. This guidance document is being
implemented immediately, but it remains subject to comment in accordance with the Agency’s
good guidance practices.
Comments may be submitted at any time for Agency consideration. Submit written comments to
the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov.
All comments should be identified with the docket number listed in the notice of availability that
publishes in the Federal Register.
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
December 2022

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Table of Contents
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 2
III. 	DEFINITIONS .................................................................................................................. 3
IV. 	RECOMMENDATIONS.................................................................................................. 4
A. 	Donor History Questionnaire............................................................................... 4
B. 	Donor Deferral ...................................................................................................... 5
C. 	Product Retrieval and Quarantine, and Notification of Consignees of Blood
and Blood Components......................................................................................... 6
D. 	Product Disposition and Labeling ....................................................................... 7
V. 	IMPLEMENTATION OF RECOMMENDATIONS .................................................... 8
VI. 	REFERENCES.................................................................................................................. 9
APPENDIX .................................................................................................................................. 11

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Recommendations to Reduce the Risk of
Transfusion-Transmitted Malaria
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
This guidance document provides you, blood establishments that collect blood and blood
components, with FDA’s recommendations to reduce the risk of transfusion-transmitted malaria
(TTM). The recommendations contained in this guidance apply to the collection of Whole
Blood and blood components, except Source Plasma. Blood establishments are not required to
assess Source Plasma donors for malaria risk (21 CFR 630.15(b)(8)). This guidance supersedes
the guidance titled “Revised Recommendations to Replace the Risk of Transfusion-Transmitted
Malaria; Guidance for Industry” dated April 2020 (April 2020 guidance).
To address the urgent and immediate need for blood and blood components during the
Coronavirus Disease 2019 (COVID-19) public health emergency, in April 2020 FDA (we)
issued revised recommendations to reduce the risk of TTM during the public health emergency.
The recommendations in the April 2020 guidance were based on the Agency’s evaluation of the
available scientific and epidemiological data on malaria risk, and data on FDA-approved
pathogen reduction devices. As stated in the April 2020 guidance, FDA expected
implementation of the revised recommendations would not be associated with any adverse effect
on the safety of the blood supply and that early implementation of the recommendations may
help to address significant blood shortages that occurred as a result of the COVID-19 public
health emergency. Further, the guidance explained that we expected that the recommendations
set forth in the revised guidance would continue to apply outside the context of the COVID-19
public health emergency, and that FDA would replace the April 2020 guidance with an updated
guidance that incorporates any appropriate changes based on public comments and our
experience with implementation.
Consequently, we are issuing this revised guidance. We are issuing this guidance for immediate
implementation. The recommendations, which are unchanged from the April 2020 guidance,
will remain in effect outside of the context of the public health emergency related to COVID-19.
Although the April 2020 guidance stated that we intended to reissue the guidance within 60 days

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following the termination of the public health emergency, we are not delaying this issuance
because the guidance represents our current thinking on the topic.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’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 Agency guidances means that something is suggested or recommended, but
not required.
II. 	BACKGROUND
Malaria is a mosquito-borne parasitic infection caused by five Plasmodia species (P. falciparum;
P. malariae; P. ovale; P. vivax; and P. knowlesi), which can also be transmitted by transfusion
of blood and blood components collected from an infected but asymptomatic donor (Refs.1-6).
Malaria was eradicated in the United States (U.S.) in the 1950s, although the Anopheles
mosquito vector exists in many states. Locally acquired mosquito-borne transmission has caused
63 small outbreaks (ranging from 1-32 malaria cases) since 1957 in the U.S., predominantly
caused by P. vivax. The last cases were reported in 2003 (Ref. 6). In contrast, malaria affects
millions of people worldwide. Plasmodia infections can be asymptomatic or can range in
severity from a mild febrile illness to life-threatening complications or death. Plasmodium
falciparum causes the most severe disease and accounts for 90% of the malarial deaths in sub-
Saharan Africa (Refs. 4-6).
TTM rarely occurs in the U.S. but remains a serious concern in transfusion medicine (Refs. 1-3).
The transfusion risk stems from asymptomatic blood donors with newly-acquired or chronic
malaria infection, which can be indolent and persist for years. The risk of TTM is currently
estimated at less than 0.1 per million red blood cell (RBC) transfusion, or about 1 case every 2
years (Ref. 7). Whole blood or RBC components are implicated in most (94%) TTM cases, with
the remainder caused by platelet components (Ref. 2). Plasma components have not been a
source of TTM (Ref. 2).
Since 1994, FDA has recommended deferral of blood donors who have had malaria or have had
possible exposure to malaria during travel to or residence in malaria-endemic countries. There is
no FDA licensed test to screen blood donors in the U.S. The donor deferral policy as previously
implemented, likely prevented cases of TTM but also resulted in a significant loss of otherwise
eligible donors (Refs. 7-9). The risk of malaria among returning travelers is low in the U.S.
About 28 million U.S. residents travel to a malaria-endemic country each year. U.S. residents
account for most (70%) of the approximately 2,000 imported malaria cases each year, while non-
U.S. residents account for the rest (30%) of the cases (Refs. 6, 7). Former residents of malaria-
endemic countries are more likely to have asymptomatic infections when they return from travel
to malaria-endemic areas because of likely prior exposure and persistence of clinical immunity to
malaria (Refs. 10, 11). Between 2000 and 2021, the reported TTM cases (n=12) in the U.S. have
implicated asymptomatic infected donors who were former residents of malaria-endemic
countries or who had a prior diagnosis of malaria; none have been linked to a traveler who was a
resident of a non-endemic country (Refs. 1, 3, 12). Consequently, deferral of prospective donors

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based on travel to malaria-endemic areas results in the loss of a large number of otherwise
eligible and healthy blood donors (Refs. 9, 13).
FDA held a scientific workshop in 2006 and Blood Product Advisory Committee (BPAC)
meetings in 2008 and 2009 to discuss strategies to minimize donor loss associated with deferrals
for malaria risk (Refs. 14, 16). In 2008, the BPAC considered different scenarios and the
possible role that antibody testing could play in identifying or reentering donors at risk for
malaria, especially those donors who had traveled to endemic areas in Mexico (Ref. 15). Several
non-endemic countries (e.g., England, Australia and France) use antibody testing to qualify
donors who report malaria risk factors, to minimize donor loss associated with travel to malaria-
endemic countries, although no test has been licensed or approved in the United States for such
use (Refs. 3, 8).
In 2009, the BPAC supported allowing blood collection, without any deferral for malaria risk,
from U.S. residents who have visited the Mexican states of Quintana Roo, which includes
Cancun and Cozumel (Ref. 16). At the time, these states contributed to the preponderance of
malaria-risk-associated donor deferral for travel to Mexico but posed an extremely low risk to
the blood supply. The risk was estimated as an absolute increase of 0.0166 infected blood unit
per year, or one TTM case in 60 years, if prospective blood donors who visited Quintana Roo
and Jalisco were allowed to donate blood without any deferral. Conversely, the change in
deferral criteria was projected to increase the donor pool by approximately 45,000 donors
(79,000 blood units) each year (Refs. 9, 16). In addition to supporting blood collection without
any deferral for malaria risk from U.S. residents who have visited Quintana Roo, the BPAC also
supported extending the proposed policy to other malaria-endemic states of Mexico that have a
low malaria transmission rate (Ref. 16). FDA incorporated the recommendations of the BPAC
into guidance, first released in June 2012.
In 2014, FDA approved pathogen reduction devices that demonstrate effective reduction of
Plasmodium falciparum for plasma or platelet components.
This guidance provides recommendations to reduce the risk of TTM, as described in section IV
below. The appendix includes a summary of the scientific rationale for these revisions.
III. 	DEFINITIONS
The following definitions, which are offered for the purpose of this guidance only, provide
explanations of terms used in the recommendations (section IV of this guidance), below:
Malaria - An infectious disease caused by a parasitic protozoan of the genus Plasmodium.
Malaria diagnosis in a prospective donor is based on a positive laboratory test indicating
Plasmodium infection, or a determination of a history of malaria made by the blood
establishment’s responsible physician.
Malaria-endemic area - Any areas with malaria where the Centers for Disease Control and
Prevention (CDC) recommends anti-malarial chemoprophylaxis in travelers in the CDC Health

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Information for International Travel (commonly known as The Yellow Book) at the time the
donor is screened. We recommend you access the “Malaria Information, by Country” table in
the Malaria chapter of The Yellow Book for the most current recommendations on anti-malarial
chemoprophylaxis. The Yellow Book is available on the CDC website at
https://wwwnc.cdc.gov/travel/page/yellowbook-home-2020.
Malaria-endemic country - Any country having an area or areas with malaria where CDC
recommends anti-malarial chemoprophylaxis in travelers in The Yellow Book at the time the
donor is screened. A country that has any malaria-endemic areas should be considered to be
malaria-endemic in its entirety.
Residence in a malaria-endemic country - For purposes of this guidance, residence is defined
as a continuous stay of longer than 5 years in a country or countries having any malaria-endemic
area (see definition above). In determining residence, consideration is by malaria-endemic
country and not by malaria-endemic area since the geographic distribution of malaria-endemic
areas may change during the period of residence, or the resident may have traveled from a non-
endemic area to an endemic area in the country during his or her stay.
Travel to a malaria-endemic area - Any travel to or through a malaria-endemic area or areas,
as identified by CDC (see definition above). The duration of travel to a malaria-endemic area is
defined as more than 24 hours to less than 5 years. Note that a passage greater than 24 hours
through a malaria-endemic area while on route to a malaria-free area is considered a sufficient
possible exposure to trigger donor deferral. Common examples of such possible exposure
include passage through a malaria-endemic area to visit a tourist resort in a malaria-free area, or
passage through a malaria-endemic area to board a cruise ship, or on-shore excursions into a
malaria-endemic area when traveling on a ship. Travel to or through a malaria-free area within a
malaria-endemic country does not constitute travel to a malaria-endemic area.
IV. 	RECOMMENDATIONS
The recommendations in this guidance for screening blood donors for malaria risk and for
implementing pathogen reduction of indicated blood components are based on the current
epidemiological data on malaria and the risk of TTM, and on the availability of FDA-approved
pathogen reduction devices.
A. 	Donor History Questionnaire
1. 	We recommend that your donor history questionnaire, including the full-
length and abbreviated donor history questionnaires, and accompanying
materials incorporate the recommendations provided in this document.
You must update your standard operating procedures to reflect any
changes (21 CFR 606.100(b)).

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2. 	We recommend that the donor history questionnaire include the following
elements to assess prospective donors for malaria risk (note definitions in
section III of this guidance):
a. 	A history of malaria in the past three years;
b. 	A history of prior residence in a malaria-endemic country;
c. 	A history of travel to a malaria-endemic area in the past three
months; and
d. 	A history of travel to a malaria-endemic area in the past three
years, if previously a resident of a malaria-endemic country.
B. 	Donor Deferral
In accordance with 21 CFR 630.10, regarding the factors that determine the eligibility of
a donor, we provide the following recommendations:
1. 	Travel to a malaria-endemic area by residents of non-endemic countries
We recommend that you defer for 3 months after the last departure from a
malaria-endemic area (as defined in section III of this guidance) a donor who is a
resident of a non-endemic country and who has traveled to or through any
malaria-endemic area, irrespective of whether the donor received malaria
chemoprophylaxis. We recommend that after the 3-month deferral period, the
donor may be eligible to donate, provided the donor has been free from malaria
during this period and meets all other donor eligibility criteria.
Alternatively, the Director of the Center for Biologics Evaluation and Research
(CBER) is providing an alternative procedure under 21 CFR 640.120(b) to the
provisions in 21 CFR 630.10(a) and (h). Specifically, under this alternative
procedure, you may collect platelet and/or plasma components from a donor who
is a resident of a non-endemic country and who has traveled to or through a
malaria endemic-area without a deferral period, provided the blood components
are pathogen-reduced using an FDA-approved pathogen reduction device
effective against Plasmodium falciparum, according to the manufacturer’s
instructions for use, and the donor meets all other donor eligibility criteria.
2. 	Prior residence in a malaria-endemic country
We recommend that you defer for 3 years a donor who had been a prior resident
(as defined in section III of this guidance) in a malaria-endemic country. We
recommend that after the 3-year deferral period, the donor may be eligible to
donate provided the donor has been free from malaria during this period and
meets all other donor eligibility criteria. Note that the Director of CBER has not

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authorized pathogen reduction as an alternative procedure to the 3-year deferral
for such donors.
3. 	Travel to a malaria-endemic area by prior residents of a malaria-endemic
country
a. 	We recommend that you defer for 3 years after a visit to a malaria-
endemic area a donor who is a prior resident of a malaria-endemic
country (as defined in section III of this guidance) and who has been a
resident of non-endemic countries for less than 3 consecutive years.
We recommend that after the 3-year deferral period, the donor may be
eligible to donate, provided the donor has been free from malaria
during this period and meets all other donor eligibility criteria. Note
that the Director of CBER has not authorized pathogen reduction as an
alternative procedure to the 3-year deferral for such donors.
b. 	We recommend that if a prior resident of a malaria-endemic country
returns to a malaria-endemic area after residence for 3 or more years
consecutively in non-endemic countries, that you defer that donor for 3
months from the time that they return to the non-endemic country. We
recommend that after the 3-month deferral period, the donor may be
eligible to donate, provided the donor has been free from malaria
during this period and meets all other donor eligibility criteria.
Alternatively, the Director of CBER is providing an alternative
procedure under 21 CFR 640.120(b) to the provisions in 21 CFR
630.10(a) and (h). Specifically, under this alternative procedure, you
may collect platelet and/or plasma components from a donor who is a
prior resident of a malaria-endemic country who returns to a malaria-
endemic area after residence for 3 or more years consecutively in non-
endemic countries without a deferral period, provided the blood
components are pathogen-reduced using an FDA-approved pathogen
reduction device effective against Plasmodium falciparum, according
to manufacturer’s instructions for use, and the donor meets all other
donor eligibility criteria.
4. 	History of malaria
We recommend that you defer for 3 years a donor who has a history of malaria.
We recommend that after the 3-year deferral period, the donor may be eligible to
donate, provided the donor has been free from malaria during this period while
residing in a non-endemic country and meets all other donor eligibility criteria.
Note that the Director of CBER has not authorized pathogen reduction as an
alternative procedure to the 3-year deferral for such donors.
C. 	Product Retrieval and Quarantine, and Notification of Consignees of Blood

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and Blood Components
We recommend that you take the following actions if you determine that blood or blood
components have been collected from a donor who should have been deferred according
to the recommendations in section IV.B of this guidance.
1. 	If you collected cellular blood components (e.g., RBCs, platelets) intended
for transfusion or for further manufacturing from a donor who should have
been deferred according to the recommendations in section IV.B of this
guidance, we recommend that you quarantine any undistributed in-date
cellular blood components collected from that donor.
2. 	If you distributed cellular blood components intended for transfusion or
for further manufacturing collected from a donor with a clinical history of
malaria who should have been deferred according to the recommendation
in section IV.B.4 of this guidance, we recommend that you notify
consignees to retrieve and quarantine the in-date cellular blood
components collected from that donor.
Additionally, in this situation, if cellular blood components have been
transfused, you should encourage consignees to notify the transfusion
recipient’s physician of record regarding the need for monitoring of the
recipient for a possible malaria infection for a period of 3 months post-
transfusion.
3. 	If you distributed cellular blood components intended for transfusion
collected from a donor who should have been deferred for malaria-risk
associated with travel or prior residence according to recommendations in
sections IV.B.1-3 of this guidance, we recommend that you notify
consignees to retrieve and quarantine the in-date cellular blood
components collected from that donor.
4. 	If you collected acellular blood components (i.e., frozen plasma products)
intended for transfusion or for further manufacturing from a donor who
should have been deferred according to the recommendations in section
IV.B of this guidance, we recommend that you quarantine any
undistributed in-date acellular blood components collected from that
donor. (Note that based on the very low risk for transmission of malaria,
we are not recommending notification of consignees if you distributed
such acellular products.)
D. 	Product Disposition and Labeling
1. 	We recommend that you destroy or relabel blood components that were
collected from a donor who should have been deferred according to the
recommendations in section IV.B of this guidance. If you relabel the

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blood components they may be released for research.
2. 	You should use the following statements to prominently relabel the blood
components:
a. 	“NOT FOR TRANSFUSION: Collected From A Donor
Determined To Be At Risk For Infection With Malaria Parasites”
and
b. 	“Caution: For Laboratory Research Only”
V. 	IMPLEMENTATION OF RECOMMENDATIONS
Licensed blood establishments must report changes to their approved license to FDA in
accordance with 21 CFR 601.12. If a licensed blood establishment has already adopted the
recommendations contained in this guidance (e.g., because the blood establishment adopted the
recommendations in the April 2020 guidance) and reported the changes to FDA in accordance
with 21 CFR 601.12, then additional reporting is not required. However, licensed blood
establishments making changes for the first time in accordance with the recommendations in this
guidance must report these changes to FDA in accordance with 21 CFR 601.12, specifically:
1. 	Licensed blood establishments that implement a version of the DHQ and accompanying
materials prepared by the AABB Donor History Task and found acceptable by FDA must
report the changes to FDA in an annual report under 21 CFR 601.12(d), noting the date
the process was implemented.
2. 	Licensed blood establishments that revise their own DHQs and accompanying materials
to reflect the recommendations in this guidance must report the change to FDA in a
Changes Being Effected (CBE) Supplement under 21 CFR 601.12(c)(5) (see 21 CFR
601.12(a)(3)). The blood and blood components collected using the change may be
distributed immediately upon receipt of the supplement by FDA.
Include the following information in your CBE Supplement:
a. 	Form FDA 356h “Application to Market a New or Abbreviated New Drug, or
Biologic for Human Use;”
b. 	Cover letter describing the request and contents of the supplement; and,
c. 	The DHQ and accompanying document(s). Please highlight the modifications.

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VI. 	REFERENCES
1. 	Katz, L.M. and Spencer, B.R., Travel and related health history: Malaria, prions and
other transfusion-transmissible diseases. In: Eder A, Goldman M eds. Screening Blood
Donors with the Donor History Questionnaire, Bethesda, MD: AABB Press, 2019.
2. 	Mungai, M., et al., Transfusion-transmitted malaria in the United States from 1963
through 1999. New England Journal of Medicine 2001; 344:1973-1978.
3. 	O’Brien, S.F., et al. The epidemiology of imported malaria and transfusion policy in 5
non-endemic countries, Transfusion Medicine Reviews 2015; 29:162-171.
4. 	Mace, K.E., and Arguin, P.M., Malaria Surveillance — United States, 2014. MMWR
Surveill Summ 2017; 66 (No. SS-12):1–24. DOI:
https://www.cdc.gov/mmwr/volumes/66/ss/ss6612a1.htm
5. 	Mace, K.E., et al., Malaria Surveillance – United States, 2015. MMWR Surveill Summ.
2018; 67(No. SS-7):1–28. DOI:
https://www.cdc.gov/mmwr/volumes/67/ss/ss6707a1.htm?s_cid=ss6707a1_w
6. 	Mace, K.E., et al., Malaria Surveillance — United States, 2016. MMWR Surveill Summ
2019; 68 (No. SS-5):1–35. DOI:
https://www.cdc.gov/mmwr/volumes/68/ss/ss6805a1.htm?s_cid=ss6805a1_w
7. 	Spencer, B., et al., Risk for malaria in United States donors deferred for travel to malaria-
endemic areas. Transfusion 2009; 49 (11):2335-2345.
8. 	Reesink, H.W., et al. The use of malaria antibody tests in the prevention of transfusion-
transmitted malaria, Vox Sanguinis 2010; 98:468-478
9. 	Spencer, B., et al., for the NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II),
Deconstructing the risk for malaria in the United States donors deferred for travel to
Mexico, Transfusion 2011; 51:2398-2410.
10. 	Liljander, A., et al., Influences of intermittent preventive treatment and persistent
multiclonal Plasmodium falciparum infections on clinical malaria risk. PLoS One 2010;
5 (10):e13649.
11. 	Doolan, D.L., et al., Acquired immunity to malaria. Clin. Microbiol. Reviews, 2009; 22
(1):13-36.
12. 	Stubbs, L., et al. Transfusion-Transmitted Malaria: Two Pediatric Cases From the United
States and Their Relevance in an Increasingly Globalized World. J. Ped. Infect Dis Soc.
2021; 10(12):1092: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719612/.
13. 	Nguyen. M.L., et al., Analyzing actual risk in malaria-deferred donors through selective
serologic testing. Transfusion 2013; 53:1736-1743.

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14. 	FDA Workshop “Testing for malarial infections in blood donors,” July 12, 2006. FDA
Blood Products Advisory Committee “Testing for malarial infections in blood donors,”
July 13, 2006. https://wayback.archive-
it.org/7993/20170404051615/https://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-
4226t1.pdf.
15. 	FDA Blood Products Advisory Committee “Options for blood donor screening and
reentry for malaria.” September 11, 2008. https://wayback.archive-
it.org/7993/20170404042917/https://www.fda.gov/ohrms/dockets/ac/08/transcripts/2008-
4379T2_1.htm.
16. 	FDA Blood Products Advisory Committee “Blood Donor Deferral for Malaria Risk
Associated with Travel to Mexico.” November 16, 2009. https://wayback.archive-
it.org/7993/20170113022624/http://www.fda.gov/downloads/AdvisoryCommittees/Com
mitteesMeetingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCom
mittee/UCM193385.pdf.

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APPENDIX
Table Summary of Recommendations
Donor History
Recommendations for Donor
Deferral or Pathogen
Reduction (PR)
Travel to a malaria-endemic
area (resident of a non-
endemic country)
3 months or PR
Resident of a malaria-
endemic country
3 years
Travel to a malaria-endemic
area (resident of a malaria-
endemic country) – less than
3 consecutive years in non-
endemic country
3 years
Travel to a malaria-endemic
area (resident of a malaria-
endemic country) – 3 or more
consecutive years in non-
endemic country
3 months or PR
Diagnosis of malaria 	3 years
SCIENTIFIC BASIS FOR RECOMMENDATIONS
The scientific basis and further explanation for the recommendations in section IV of this
guidance are as follows:
A. 	Travel to malaria endemic area by residents of a non-endemic country
• 	We recommend a 3-month deferral period for a donor who is a resident of a non-
endemic country and who has traveled to or through a malaria-endemic area (whether
or not the donor received malaria prophylaxis). The recommendation is based on the
malaria surveillance reports by CDC showing that out of 3,696 imported malaria
cases reported between 2014-2016 for which the date of arrival and the onset of
illness was known, 86% (3,187) developed clinical symptoms within 1 month of
return to the U.S. and 94% (3,476) developed clinical symptoms within 3 months
(Refs. 4-6). The-3-month deferral for residents of non-endemic countries applies to
the date of the last departure from the endemic area.

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• 	Based on the definition in section III of this guidance of “travel to a malaria endemic
area” and epidemiological data on malaria risk, FDA does not currently recommend
deferral of donors who have traveled to the Mexican states of Quintana Roo and
Jalisco. Please note that the designation of malaria-endemic areas in Mexico or in
any malaria-endemic country is subject to change based on the most updated malaria
transmission information with respect to that area, as listed in The Yellow Book. For
example, if malaria transmission in these states changes and anti-malarial
chemoprophylaxis is recommended by CDC, then the donor deferral
recommendations would encompass donors who travel to these areas.
• 	FDA has approved pathogen reduction devices that demonstrate effective reduction of
Plasmodium falciparum for plasma or platelet components, when used according to
their instructions for use. Under the alternative procedure issued by the Director of
CBER, such devices can be used as an alternative to donor deferral and allow
collection of components from otherwise-eligible donors who are residents of malaria
non-endemic countries and have traveled to a malaria-endemic area.
B. 	Prior residence in a malaria-endemic country
• 	The recommendation for a 3-year deferral of a donor following residence in a
malaria-endemic country is based on the possible presence of low-grade parasitemia
in individuals with clinical immunity to malaria, or in individuals with a chronic
malaria infection who have not received definitive treatment after departure from the
malaria-endemic area. Although it is not known how long parasitemia can last in
such persons, it is believed that most will either develop clinical malaria or else
resolve their infection over time. This is because anti-malarial immunity is thought to
wane in the absence of repeated infections. Data reported by CDC showed that out of
4,229 reported cases of malaria in residents born in a malaria-endemic country, only 7
cases (0.2%) had an episode of clinical malaria more than three years after the patient
had left a malaria-endemic country (Ref. 2). These data suggest that a deferral period
of 3 years is adequate for resolution of parasitemia in most cases.
• 	The Director of CBER has not authorized pathogen reduction as an alternative
procedure to the 3-year deferral for such donors because of the higher potential risk of
malaria. In addition, all reported TTM cases in the U.S. have implicated
asymptomatic infected donors who were former residents of malaria-endemic
countries or who had a prior diagnosis of malaria.
C. Travel to a malaria-endemic area by prior residents of a malaria-endemic country
• 	The recommendation for a 3-year deferral after a visit to a malaria-endemic area for a
donor who is a prior resident of a malaria-endemic country (as defined in section III
of this guidance) and who has been a resident of non-endemic countries for less than
3 consecutive years is based on the possible presence of low-grade parasitemia in
individuals with clinical immunity to malaria, or in individuals with a chronic malaria

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infection who have not received definitive treatment after departure from the malaria-
endemic area.
• 	The Director of CBER has not authorized pathogen reduction as an alternative
procedure to the 3-year deferral for such donors because of the higher potential risk of
malaria. In addition, all reported TTM cases in the U.S. have implicated
asymptomatic infected donors who were former residents of malaria-endemic
countries or who had a prior diagnosis of malaria.
• 	We recommend a 3-month deferral from the time of return to a non-endemic country
for a donor who was a prior resident of a malaria-endemic country and who had not
traveled to a malaria-endemic area for 3 or more consecutive years preceding the
most recent travel to a malaria-endemic area. This recommendation is based on
information indicating that continued exposure to malaria parasites is necessary to
maintain clinical immunity (Refs. 10-11). Consequently, we believe it is a reasonable
safeguard to conclude that after 3 or more continuous years of residence in a non-
endemic country, the majority of prior residents of malaria-endemic areas will not
maintain their clinical immunity. Thus, we recommend that after 3 years of
continued residence in a non-endemic country, a prior resident of a malaria-endemic
country may be considered to be a resident of a non-endemic country for purposes of
screening blood donors. We recommend that such individuals should be deferred for
3 months after each return from travel to a malaria-endemic area consistent with the
deferral for travelers from non-endemic countries.
Under the alternative procedure issued by the Director of CBER, pathogen reduction
devices can be used as an alternative to donor deferral for this group of donors.
D. Product retrieval and consignee notification
The recommendation that consignee notification include instructions for notification
of the transfusion recipient’s physician of record regarding the need for monitoring of
the recipient for a possible malaria infection for a period of 3 months post-transfusion
(section IV.C.2) is based on the analysis of incubation periods in 57 cases of
transfusion-transmitted malaria in the U.S., in which the maximum period observed
between transfusion and onset of clinical symptoms was 90 days (range 8 to 90 days)
(Ref. 2). This recommendation is limited to the highest risk circumstance, namely
transfusion of a unit from an ineligible donor who had a clinical history of malaria
who should have been deferred for at least 3 years.