Guidance for Industry: Recommendations for Donor Questioning, Deferral, Reentry and Product Management to Reduce the Risk of Transfusion-Transmitted Malaria

I. Introduction

II. Background

III. Definitions

IV. Recommendations
A. Donor History Questionaire
B. Donor Deferral and Reentry
C. Product Retrieval and Quarantine, and Notification of Consignees of Blood and Blood Components
D. Product Disposition and Labeling
E. Reporting a Biological Product Deviation (BPD)

V. Additional Considerations

VI. Implementation of Recommendations

VII. References

Appendix

Footnotes

VIII. For More Information

Reference Information:

• About this guidance document
• To obtain copies of this document
• For questions regarding this document
• FDA office that authored this guidance

August 2013

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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 malariaade by the blood establishment’s Medical Director.  For additional information regarding malaria and its associated symptoms, visit the Centers for Disease Control and Prevention (CDC) website at http://www.cdc.gov/malaria/.  

Malaria-endemic area – Any areas with malaria where CDC recommends anti-malarial chemoprophylaxis in travelers in the most current version of 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 http://wwwnc.cdc.gov/travel/page/yellowbook-2012-home.htm.

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

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SCIENTIFIC RATIONALE AND FURTHER EXPLANATION FOR THE RECOMMENDATIONS

The scientific basis and further explanation for the recommendations in section IV of this guidance are as follows:

• The recommendation for a 3-year deferral of a donor following residence in a malaria-endemic country (recommendations B.2. and B.3.b.) is based on the possible presence of low-grade parasitemia in individuals with clinical immunity to malaria, or 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 (though not all) 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 foreign-born residents, 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. 3).  These data suggest that a deferral period of 3 years would be adequate for resolution of parasitemia in most cases.  This recommendation will be reconsidered periodically based on new scientific data.
• Recommendation B.3.a of a 1-year 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), is based on the malaria surveillance reports by CDC showing that out of 2,167 imported malaria cases reported between 2008-2010 for which the date of arrival and the onset of illness was known, only 2 (0.09%) experienced clinical malaria more than 1 year after their return to the U.S. (Refs. 14-16).  The 1-year deferral for residents of non-endemic countries applies to the last departure from the endemic area.
• Blood centers should use the new definition of malaria-endemic area (see section III of this guidance) in deciding whether a donor had traveled to a malaria-endemic area.

Based on the current epidemiological data and the definition of malaria-endemic area in this guidance, FDA does not currently recommend deferral of donors who have traveled to the Mexican states of Quintana Roo and Jalisco; thus, these donors, if otherwise eligible, may donate.  Please note that the designation of malaria-endemic areas in Mexico or in any malaria endemic country and accordingly, a recommendation for donor deferral, are 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.

• The recommendation for a one year 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 consecutive years preceding the most recent travel to a malaria-endemic area (recommendation B.3.c.) is based on information indicating that continued exposure to malaria parasites is necessary to maintain clinical immunity (Refs. 17, 18).  Consequently, we believe it is a reasonable safeguard to assume 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, after 3 years of continued residence in a non-endemic country, a prior resident of a malaria-endemic country may be treated as a resident of a non-endemic country.  Such individuals should be deferred for only 1 year after each return from travel to a malaria-endemic area consistent with the deferral for travelers from non-endemic countries.  
• In many parts of the world, transmission of malaria and dengue can occur in the same area.  FDA is aware that under the new definition of a malaria-endemic area, potentially eligible donors may have traveled to areas where dengue virus is transmitted.  FDA is currently evaluating the risk of dengue virus infections in blood donors that are acquired either locally or elsewhere in the world, and may address this issue in future guidance. 
• The recommendation that consignee notification include instructions for notification of the transfusion recipient or 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 (recommendation 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. 3).  This recommendation is limited to the highest risk circumstance of unintentional release of a unit from a donor at risk of malaria, namely a unit from a donor who had a clinical history of malaria who may not have been treated or who failed to be deferred for at least 3 years.
• The recommendation to allow the use of acellular blood components inadvertently collected from a donor who was later determined to be at risk for malaria to make injectable products is based on the knowledge that licensed plasma derivatives do not transmit malaria.  In addition, notification of consignees is not recommended and reporting of biological product deviation is not required for acellular components inadvertently collected and distributed from a donor at risk for malaria because of the lack of a documented case of transfusion-transmitted malaria from acellular blood components.  According to a CDC surveillance study (Ref. 3), 93 cases of transfusion transmitted malaria were reported in the U.S. from 1963-1999.  Among the 70 cases for which information was available, the following blood components were implicated: whole blood (63%); red cells (31%); and platelets (6%).  Plasma components were not shown as a source of transfusion-transmitted malaria.

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This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic.  It does not create or confer any rights for or on any person and does not operate to bind FDA or the public.  You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.  If you want to discuss an alternative approach, contact the appropriate FDA staff.  If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.

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If you have questions regarding this guidance and FDA policies for implementing acceptable aDHQ documents, contact OCOD at the phone numbers or e-mail address listed above.

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U.S. Department of Health and Human Services
Food and Drug Administration

• Center for Biologics Evaluation and Research

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• Guidance for Industry: Recommendations for Donor Questioning, Deferral, Reentry and Product Management to Reduce the Risk of Transfusion-Transmitted Malaria – August 2013 (PDF – 100KB)
  
  August 2013