Reducing Risk of Relevant Transfusion-Transmitted Infection

Revised Recommendations to Reduce
the Risk of Transfusion-Transmitted
Malaria
_______________________________
Guidance for Industry
This guidance is for immediate implementation.

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 240-402-7800, or email ocod@fda.hhs.gov, or
from the Internet at https://www.fda.gov/vaccines-blood-biologics/guidance-complianceregulatory-information-biologics/biologics-guidances or https://www.fda.gov/emergencypreparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staffand-other-stakeholders.
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
April 2020

Contains Nonbinding Recommendations

Preface
Public Comment
Given the public health emergency related to COVID-19 declared by the Department of Health
and Human Services (HHS), this guidance is being implemented without prior public comment
because FDA has determined that prior public participation for this guidance is not feasible or
appropriate (see section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C
Act) and 21 CFR 10.115(g)(2)). 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 FDA-2000-D-0187 (formerly Docket
No. 2000D-1267) and complete title of the guidance in the request.

Additional Copies
Additional copies are available from the FDA webpage titled “Coronavirus Disease 2019
(COVID-19),” available at https://www.fda.gov/emergency-preparedness-andresponse/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-otherstakeholders, and the FDA webpage titled “Search for FDA Guidance Documents” available
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
Additional copies of this guidance are also 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-bloodbiologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

Questions
For questions on the content of this guidance, contact OCOD at the phone numbers or email
address listed above.

Contains Nonbinding Recommendations

Table of Contents
I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2

III.

DEFINITIONS .................................................................................................................. 4

IV.

RECOMMENDATIONS.................................................................................................. 5
A.
B.
C.
D.

Donor History Questionnaire............................................................................... 5
Donor Deferral ...................................................................................................... 5
Product Retrieval and Quarantine, and Notification of Consignees of Blood
and Blood Components......................................................................................... 7
Product Disposition and Labeling ....................................................................... 8

V.

IMPLEMENTATION OF RECOMMENDATIONS .................................................... 8

VI.

REFERENCES ................................................................................................................ 10

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Revised 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 revised 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 (see 21 CFR 630.15(b)(8)).
This guidance supersedes the guidance dated August 2013 and updated August 2014, entitled,
“Recommendations for Donor Questioning, Deferral, Reentry and Product Management to
Reduce the Risk of Transfusion-Transmitted Malaria” (Notice of Availability, 78 FR 50421
(August 19, 2013)).
The recommendations in this revised guidance reflect the Agency’s current thinking on
recommendations for reducing the risk of TTM. Based on the Agency’s careful evaluation of the
available scientific and epidemiological data on malaria risk, and data on FDA-approved
pathogen reduction devices, FDA expects implementation of these revised recommendations will
not be associated with any adverse effect on the safety of the blood supply. Furthermore, early
implementation of the recommendations in this guidance may help to address significant blood
shortages that are occurring as a result of a current and ongoing public health emergency. In
particular, there is currently an outbreak of respiratory disease caused by a novel coronavirus.
The virus has been named “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2)
and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January
31, 2020, HHS issued a declaration of a public health emergency related to COVID-19 and

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mobilized the Operating Divisions of HHS. 1 In addition, on March 13, 2020, the President
declared a national emergency in response to COVID-19. 2
As a result of this public health emergency, there is a significant shortage in the supply of blood
in the United States, which early implementation of the recommendations in this guidance may
help to address (even though the recommendations in this guidance are broadly applicable
beyond the COVID-19 public health emergency). For this reason, this revised guidance is being
implemented without prior public comment because FDA has determined that prior public
participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the
FD&C Act and 21 CFR 10.115(g)(2)). This guidance document is being implemented
immediately, but it remains subject to comment in accordance with the Agency’s good guidance
practices.
Because this revised guidance is being issued without prior public comment in light of the
COVID-19 public health emergency, it is intended to remain in effect for the duration of this
public health emergency, including any renewals made by the HHS Secretary in accordance with
section 319(a)(2) of the Public Health Service Act (42 U.S.C. 247d(a)(2)). However, as noted,
FDA expects that the recommendations set forth in this revised guidance will continue to apply
outside the context of the current public health emergency. Therefore, within 60 days following
the termination of the public health emergency, FDA intends to revise and replace this guidance
with an updated guidance that incorporates any appropriate changes based on comments received
on this guidance and the Agency’s experience with implementation.
In general, FDA’s guidance documents, including this guidance, 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 guidance means that something is
suggested or recommended, but not required.

II.

BACKGROUND

Malaria is a mosquito-borne parasitic infection caused by Plasmodia species (P. falciparum; P.
malariae; P. ovale; or P. vivax), 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
1
Secretary of Health and Human Services Alex M Azar, Determination that a Public Health Emergency Exists. Jan.
31, 2020. (Accessible at https://www.phe.gov/emergency/news/healthactions/phe/Pages/2019-nCoV.aspx).
2
President Donald J. Trump, Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus
Disease (COVID-19). Mar. 13, 2020. (Accessible at https://www.whitehouse.gov/presidentialactions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/).

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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 nonU.S. residents account for the rest (30%) of the cases (Refs. 6, 7). Former residents of malariaendemic 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 2017, the reported TTM cases (n=11) 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). Consequently, the deferral of thousands of
prospective donors each year for travel to malaria-endemic countries is disproportionate to any
associated risk of TTM (Refs. 9, 12). To minimize donor loss, several non-endemic countries
(e.g., England, Australia, and France) use antibody testing to qualify donors who have malaria
risk factors (Refs. 3, 8).
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. 13, 14). 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). The
BPAC concluded that additional risk analyses would be needed, and that the analyses should
account for malaria risk globally and in Mexico, with and without antibody testing.
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

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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 revised recommendations to reduce the risk of TTM, as summarized in
the appendix and described in section IV below. The appendix also 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
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-2014.
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 nonendemic area to an endemic area in the country during his or her stay.

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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 you update your donor history questionnaire,
including the full-length and abbreviated donor history questionnaires, and
accompanying materials as necessary to incorporate the recommendations
provided in this document. You must update your standard operating
procedures to reflect any such changes (21 CFR 606.100(b)).

2.

We recommend that the updated 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
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

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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
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 malariaendemic 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.

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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 malariaendemic area after residence for 3 or more years consecutively in nonendemic 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
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 posttransfusion.
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D.

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.)

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
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

You may adopt the recommendations contained in this guidance once you have revised your
donor history questionnaire (DHQ), including full-length and abbreviated DHQs, and
accompanying materials as necessary to reflect the new donor deferral recommendations.
Licensed blood establishments must report changes to their approved license to FDA in
accordance with 21 CFR 601.12.
1.

Licensed blood establishments that revise their DHQs and accompanying material
must report the change to FDA in a Changes Being Effected (CBE) Supplement

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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
c. The DHQ and accompanying document(s). Please highlight the
modifications.
2.

Licensed blood establishments that implement a revised version of the DHQ and
accompanying materials prepared by the AABB Donor History Task Force or the
Plasma Proteins Therapeutic Association (PPTA) 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.

3.

Unlicensed establishments are not required to report this change to FDA.

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VI.

REFERENCES

1.

Katz LM and Spencer BR, 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, Tegtmeier, G, Chamberland, M, Parise, M. Transfusion-transmitted malaria
in the United States from 1963 through 1999. New England Journal of Medicine 2001;
344:1973-1978.

3.

O’Brien SF, Delage G, Seed CR, Pillonel J, et al. The epidemiology of imported malaria
and transfusion policy in 5 non-endemic countries, Transfusion Medicine Reviews 2015;
29:162-171.

4.

Mace KE, Arguin PM. 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 KE, Arguin PM, Tan KR. 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 KE, Arguin PM, Lucchi NW, Tan KR. 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, Steele, W, Custer, B, Kleinman, S, Cable, R, Wilkinson, S, Wright, D. Risk
for malaria in United States donors deferred for travel to malaria-endemic areas.
Transfusion 2009; 49 (11):2335-2345.

8.

Reesink HW, Panzer S, Wendel S, Levi JE, et al. The use of malaria antibody tests in the
prevention of transfusion-transmitted malaria, Vox Sanguinis 2010; 98:468-478

9.

Spencer B, Kleinman S, Custer B, Cable R, 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, Chandramohan, D, Kweku, M, Olsson, D, Montgomery, SM, Greenwood,
B, Farnert, A. Influences of intermittent preventive treatment and persistent multiclonal
Plasmodium falciparum infections on clinical malaria risk. PLoS One 2010; 5
(10):e13649.

11.

Doolan, DL, Dobano, C, Baird, JK. Acquired immunity to malaria. Clin. Microbiol.
Reviews, 2009; 22 (1):13-36.

12.

Nguyen ML, Goff T, Gibble J, Steele WR, Leiby D. Analyzing actual risk in malariadeferred donors through selective serologic testing. Transfusion 2013; 53:1736-1743.

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13.

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.archiveit.org/7993/20170404051615/https://www.fda.gov/ohrms/dockets/ac/06/transcripts/20064226t1.pdf

14.

FDA Blood Products Advisory Committee “Options for blood donor screening and
reentry for malaria.” September 11, 2008. https://wayback.archiveit.org/7993/20170404042917/https://www.fda.gov/ohrms/dockets/ac/08/transcripts/20084379T2_1.htm

15.

FDA Blood Products Advisory Committee “Blood Donor Deferral for Malaria Risk
Associated with Travel to Mexico.” November 16, 2009. https://wayback.archiveit.org/7993/20170113022624/http://www.fda.gov/downloads/AdvisoryCommittees/Com
mitteesMeetingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCom
mittee/UCM193385.pdf

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APPENDIX
Table: Comparison of Recommendations in 2013 (Updated 2014) and 2020 Guidance

Donor History

Travel to a malaria-endemic
area (resident of a nonendemic country)
Resident of a malariaendemic country
Travel to a malaria-endemic
area (resident of a malariaendemic country) – less than
3 consecutive years in nonendemic country
Travel to a malaria-endemic
area (resident of a malariaendemic country) – 3 or more
consecutive years in nonendemic country
Diagnosis of malaria

Recommendations for Donor
Deferral or Pathogen
Reduction (PR)
August 2013 Guidance
(Updated August 2014)

Recommendations for Donor
Deferral or Pathogen
Reduction (PR)
2020 Guidance

1 year

3 months or PR

3 years

3 years

3 years

3 years

1 year

3 months or PR

3 years

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
•

A new recommendation in this guidance (March 2020) changes the 12-month
deferral period to a 3-month deferral period for a donor who is a resident of a nonendemic 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

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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.
•

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 antimalarial 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, which has not changed from the version of this guidance
issued in 2013, 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 malariaendemic 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.

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

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Contains Nonbinding Recommendations
3 consecutive years, which has not changed from the version of this guidance issued
in 2013, 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.
Note that 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.
•

A new recommendation in this guidance (March 2020) changes the 12-month
recommended deferral to a 3-month recommended deferral from the time of return to
a non-endemic country of 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 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.

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