Guidance for Industry

Recommendations for Donor

Questioning Regarding Possible

Exposure to Malaria

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this document should be submitted by the date

provided in the Federal Register notice announcing the availability of the draft guidance.

Submit comments to Documents Management Branch (HFA-305), Food and Drug

Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments

should be identified by the docket number listed in the notice of availability

that publishes in the Federal Register.

Additional copies of this draft guidance are available from the Office of Communication,

Training and Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Rockville, MD

20852-1448, or by calling 1-800-835-4709 or (301) 827-1800, or from the Internet at

http://www.fda.gov/cber/guidelines.htm

For questions on the content of this draft guidance contact Mark Heintzelman, Ph.D., by

telephone at (301) 827-3524, or by telefax at (301) 827-3534.

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Biologics Evaluation and Research (CBER)

June 2000
Draft – Not for Implementation

i

TABLE OF CONTENTS

[Note: page numbering may vary for documents distributed electronically.]

I. INTRODUCTION..................................................................................................... 1

II. BACKGROUND ....................................................................................................... 1

III. RECOMMENDATIONS......................................................................................... 3

IV. IMPLEMENTATION .............................................................................................. 4

V. REFERENCES......................................................................................................... 5
Draft – Not for Implementation

GUIDANCE FOR INDUSTRY1

Recommendations for Donor Questioning

Regarding Possible Exposure to Malaria

I. INTRODUCTION

This guidance document provides the recommendations of the Food and Drug

Administration (FDA) for donor questioning regarding travel to vacation resorts located in

malarious regions. These recommendations apply only to donations containing intact red

blood cells or platelets. Donations used for preparing plasma, plasma components or

derivatives devoid of intact red blood cells or platelets are excluded. In addition, the term

“resident” is being defined for the purposes of malarial deferral, to be a person that has

resided in a malarious area for five years or longer. This guidance document, when

finalized, will replace the recommendations in the guidance entitled, "Recommendations for

Deferral of Donors for Malaria Risk" dated July 26, 1994, for deferral of blood donors for

malaria risk.

II. BACKGROUND

Surveillance studies conducted by the Centers for Disease Control and Prevention (CDC)

since 1974 indicated no change in the frequency of transfusion-transmitted malaria,

estimated at 0.25 cases per million blood units collected, compared with the experience

under previous donor deferral practices (Ref. 1). Nevertheless, more recently obtained

scientific data led some researchers and the American Association of Blood Banks to

reexamine the standards then in place (Ref. 2, 3) and to propose revised standards for donors

at risk for malaria.

FDA brought this issue to public discussion at the June 29, 1993, meeting of its Blood

Products Advisory Committee. Subsequently, FDA issued guidance to blood establishments

regarding the deferral of blood donors at increased risk for malaria in a guidance of July 26,

1994, entitled, “Recommendations for Deferral of Donors for Malaria Risk.” That guidance

states that permanent residents of countries where malaria is not endemic and who travel to

an area considered endemic for malaria by the Malaria Branch, CDC, Department of Health

and Human Services, should not be accepted as donors of Whole Blood and blood

components for one year after departure from the endemic area, regardless of whether or not

they have received anti-malarial chemoprophylaxis. Currently, there are no approved tests

to screen donated blood for malaria, careful questioning is essential for identifying

prospective donors at risk for transmitting malaria. Blood establishment personnel should

 

1

 This guidance document represents FDA’s current thinking on malarial risks for prospective blood donors.

It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An

alternative approach may be used if such approach satisfies the requirements of the applicable statute,

regulations, or both.
Draft – Not for Implementation

2

carefully elicit the necessary information regarding travel and disease history in order to

defer those at risk. Two recently reported fatal cases of transfusion-acquired malaria

underscore the need to maintain vigilance in deferral of at-risk donor’s (Ref. 4, 7).

Four species of plasmodia infect humans: P. falciparum, P. malariae, P. ovale, and P. vivax.

They are transmitted by infected female Anopheles mosquitoes. The malarial organisms

have a worldwide distribution and are endemic in areas with Anopheles mosquitoes and a

human reservoir (Ref. 5). At the present time, malaria has essentially been eradicated from

most of Europe, the United States, Australia, and Japan. It has not been naturally

transmitted in climates such as exist in Canada, the Nordic countries, and northern Russia.

The risk of developing malaria is directly proportional to the density of the human reservoir,

the density of the vector population, and the resulting amount of exposure. In general, even

in endemic countries, there is little risk at altitudes above 5000 feet of elevation, and less in

more temperate climates. Urban areas are generally safer than rural ones (Ref. 5). Since

female Anopheles mosquito activity occurs primarily from dusk to dawn, risk of exposure to

malaria is highest at this time period. Nonetheless, it is impossible to fully identify each and

every individual's exposure in an endemic area and the safety level required for the nation’s

blood supply necessitates that visitors to areas endemic for malaria be deferred regardless of

the time of day of exposure. The Blood Products Advisory Committee discussed this issue

at their June 1999 meeting, and voted against allowing travelers to endemic areas to donate

blood, regardless of the time of day for the travel.

FDA has received requests for clarification regarding whether exclusion of travelers as

blood donors, should include visitors to resorts located in rural areas in Mexican states

considered at risk for malaria by the CDC (as listed in CDC’s Health Information for

International Travelers, known as the “CDC Yellow Book” or on CDC’s web site,

www.CDC.gov). This issue was discussed at a public meeting of FDA’s Blood Products

Advisory Committee on December 12, 1996. Since that time, FDA has reviewed the

available information on risk of malaria at Mexican resorts. CDC provides information

regarding these geographical areas and the risk of malaria.

Blood establishments are advised that the “CDC Yellow Book” is revised periodically by

the CDC, and blood establishment Standard Operating Procedures and deferral practices

should keep pace with such revisions. The level of safety required for the blood supply

necessitates that standards be set such that risks for malaria that may not require

chemoprophylaxis for travelers may result in deferral as a blood donor.
Draft – Not for Implementation

3

III. RECOMMENDATIONS

FDA's recommendations for deferral of blood donors at increased risk for malaria are as

follows:

1. Permanent residents of non-endemic countries who travel to an area considered

endemic for malaria by the Malaria Epidemiology Section, CDC, should not be

accepted as donors of Whole Blood and blood components, including platelets, prior

to one year after departure from the endemic area. After one year has passed since

departure from the malarious area, such otherwise suitable prospective donors may

be accepted provided that they have been free of unexplained symptoms suggestive

of malaria and regardless of whether or not they have received antimalarial

chemoprophylaxis.

2. Prospective donors who have had malaria and received an appropriate treatment

should be deferred for three years after becoming asymptomatic.

3. Persons that have previously resided in endemic countries and now reside in the

United States, such as immigrants, refugees, citizens, or residents (for at least five

years) of endemic countries should not be accepted as donors of Whole Blood or

blood components, including platelets, prior to three years after departure from the

area. After the three year period, otherwise suitable prospective donors may be

accepted if they have remained free of unexplained symptoms suggestive of malaria.

4. Persons that may possess a partial acquired immunity to malaria, such as those

that have previously resided in a malarious region for at least five years (immigrants,

refugees, citizens, persons who have been or who are residents of endemic

countries), should not be accepted as donors of Whole Blood or blood components,

including platelets, for a period of three years since their last visit to a malarious

region.

5. The following questions should be added to the donor questionnaire:

a) “Were you born in the United States?”

If the answer is yes, the donor should be asked,

b) “Have you traveled outside of the United States in the last three years?”

If so, determine if the area visited was a malarious area that should result in donor deferral.

If the answer to the question “Were you born in the United States” is no, the

donor should be asked,

i) “When did you arrive in the United States?” and
Draft – Not for Implementation

4

ii) “Since your arrival, have you traveled outside the United States?”

If the answer to the question in “5a” (above) is yes, or if in question “ii”

(above) it is determined that the prospective donor has traveled out of the

United States, follow-up questions should be asked to determine the country

or geographical regions that have been visited.

Blood collection facilities should further question the prospective donor regarding exposure

history to better ascertain the actual risk of exposure to malaria using the information

contained in the BACKGROUND section of this document. If questions persist about

whether a prospective donor traveled to a malaria endemic area, call the Malaria

Epidemiology Section, CDC, at (770) 488-7788. For other questions concerning malarial

risk and donor suitability, please contact the Division of Emerging and Transfusion

Transmitted Diseases, Center for Biologics Evaluation and Research, FDA at (301) 827-

3011.

When more than one deferral period applies to a donor, the longest period of deferral

should go into effect.

IV. IMPLEMENTATION

The recommendations contained in this guidance may be implemented immediately without

prior approval from the FDA. Under 21 CFR 601.12 licensed establishments implementing

these recommendations should submit by official correspondence a statement in their annual

report indicating the date that the revised standard operating procedures, consistent with

these recommendations, have been established and implemented.

Questions concerning these recommendations should be directed to the Division of Blood

Applications, Office of Blood Research and Review, Center for Biologics Evaluation and

Research, FDA at (301) 827-3524, FAX (301) 827-3534.
Draft – Not for Implementation

5

V. REFERENCES

1. Guerrero I, Weniger B, Schultz M. Transfusion malaria in the United States, 1972-

1981. Ann Intern Med 1983;99:221-226.

2. Sazama K. Prevention of transfusion-transmitted malaria: Is it time to revisit the

standards? Transfusion 1991;31:786-788.

3. Nahlen B, Lobel H, Cannon S, Campbell C. Reassessment of blood donor selection

criteria for United States travelers to malarious areas. Transfusion 1991;31:798-804.

4. US Army Medical Surveillance Activity. Transfusion-transmitted P. falciparum

malaria. Medical Surveillance Monthly Report (MSMR), 4:2(Feb/Mar), 1998, 13-14.

5. Westphal R: Transfusion-Transmitted Malarial Infections. In Smith, D and Dodd, R

(eds.), Transfusion Transmitted Infections, ASCP Press, Chicago IL, 1991, pp. 167-180.

6. Malaria Surveillance - United States, MMWR 2/26/99, Vol 48, No.SS1, CDC

Surveillance Summaries.

7. Transfusion-Transmitted Malaria - Missouri and Pennsylvania, 1996-1998, MMWR

April 02, 1999/48(12); 253-256.