Advancing Prion Science: Guidance for the National Prion Research Program: Interim Report (2003)

U.S. forces are continually deploying around the globe. On December 31, 2001, 255,065 U.S. forces were deployed to 144 countries outside the United States (DOD Almanac, 2002), including several countries where bovine spongiform encephalopathy (BSE) has been reported and where variant Creutzfeldt-Jakob disease (vCJD) subsequently occurred. In addition, U.S. forces are frequently accompanied by their families when they are deployed on non-combat missions over an extended period. As a result, U.S. military personnel and their families deployed to countries where BSE had been reported were at increased risk of exposure to BSE-contaminated food products for several years starting in the early 1980s.

Likewise, deployed U.S. military personnel may receive blood transfusions if they are injured in combat or under other circumstances. These two factors, exposure to BSE-contaminated food and exposure to BSE-contaminated blood products, constitute the focus of this chapter.

Specifically, how much risk of exposure to BSE do U.S. forces face? Under what circumstances would that risk occur? Additionally, if a member of the U.S. forces is being treated for trauma with a blood transfusion, how much risk is there that prions are in the transfused blood? This chapter explores both sets of conditions and comments on the nature and extent of the risks.

To assess the military's risk of exposure to BSE-tainted beef products, a brief description of how food is supplied to military personnel is appropriate. All beef products supplied to U.S. forces come from approved suppliers. The forces receive a majority of their food, including beef and beef products, from U.S. producers. Food is prepared and prepackaged in a variety of ration sets served during training or combat operations. Some meals are served fresh, and regulations dictate that vendors selling food destined for troops be closely inspected and regulated.¹

Commanders of U.S. military units have the authority to purchase food products locally, including beef. A commander might authorize this if his or her troops had been eating pre-prepared rations for an extended period of time to offer variety and to maintain high morale. In that circumstance, if local beef was purchased in a country where BSE had been reported, the troops would be at risk of exposure to BSE. This practice of procurement of local beef, however, is the exception rather than the rule. Current policy prohibits the purchase of beef from a country reporting cases of BSE, but it does not prohibit the purchase of beef from other countries, so long as the source is approved by the U.S. Department of Defense (DOD) Veterinary Services. Some of this beef was purchased from the United Kingdom, Italy, Germany, and Japan before it was recognized as potentially being infected with the BSE agent.

Military personnel, as well as their families, also have access to beef products through several other outlets. The first is a commissary system. These commissaries are military supermarkets stocked primarily with food products from the United States. U.S. producers generally supply all the beef sold in these commissaries. However, in some European countries where BSE had been reported, some beef sold in commissaries was locally procured for certain periods of time. From 1980 to 1989, the monthly foreign beef procurement from non-U.S.

suppliers averaged 2.5 million pounds. Of this amount, 35 percent was from the United Kingdom and 65 percent was from other European countries. Of the product from the United Kingdom, approximately 300,000 pounds was delivered each month to commissary stores north of the Alps (Germany, Belgium, The Netherlands, and the United Kingdom) and approximately 575,000 pounds was delivered each month to commissary stores south of the Alps (Italy, Spain, Greece, and Turkey). Supply contracts for 112 stores located on 21 delivery routes were written on a monthly basis. Thus, the source of supplies for a specific store could and did change monthly. Records of specific delivery dates and locations no longer exist. This made it impossible to determine which stores received beef from the United Kingdom, but it must be assumed that all stores received some product from that country. These contracts were for carcass beef, which was split into forequarters and hindquarters at the packinghouse and further processed into cuts for retail sale in the meat market of the commissary store.

In 1990 the Beef to Europe Program was initiated for commissary stores north of the Alps. This program, which was congressionally mandated and not related to BSE, entailed the shipment of boxed beef (vacuum-packaged wholesale cuts of beef) of U.S. origin to Europe. During a supply failure, beef was purchased on an emergency basis within Europe. Of these emergency contracts, 99 percent were given to German meat packers. All commissary stores within the United Kingdom with the exception of the commissary in Edzell, Scotland, participated in the Beef to Europe Program. Shipments to the Edzell Commissary and areas south of the Alps continued to be carcass beef from the United Kingdom. These contracts converted to boxed beef in 1994. After March 1996, all procurement of beef from the United Kingdom ended, and in March 2000, all procurement of European beef stopped.

Beef products are also sold to members of the U.S. military and their families at post exchanges (PXs), which are located on U.S. military posts and bases. The Army and Air Force Exchange Service (AAFES), which manages the exchange system, was not able to provide estimates of the total number of pounds of beef procured in Europe during the same time frames mentioned above. They did, however, use cuts of carcass meat and distribution procedures similar to those described above for the commissary system. AAFES food service

outlets used European beef, and approximately 20 percent of this beef was from the United Kingdom.

A third outlet for the purchase of beef by members of the U.S. military and their families is hamburger franchises. Before the reduction of troop strength in Europe, more than 50 hamburger franchises were operating as concessions. These operations used preformed patties from the United Kingdom through 1989. From 1990 to March 2000, either U.S. beef was used or beef was ground in an AAFES-operated facility in Germany by using a combination of U.S. beef and beef from European countries other than the United Kingdom. Between March 1996 and March 2000, most beef originated from European countries without cases of BSE, and some came from the United States. Since March 2000 the beef has been of U.S. or non-European origin.

Members of U.S. forces, including their family members, commonly enjoy the local culture and consume locally prepared foods while they are stationed overseas. They purchase food in local markets and dine in local eating establishments. However, the majority of food that they consume comes from either the system used to feed troops or the commissary system.

The greatest period of risk for exposure to tainted beef products occurred between 1980 and 1996 in the United Kingdom. For continental Europe that period of risk was extended beyond 1996. In the early 1980s, the BSE outbreak was not apparent, yet cattle were infected with BSE. Effective controls to prevent further contamination of the food supply were iteratively put in place first in the United Kingdom and then throughout other European countries. During that period 4,428,572 military personnel and their family members were potentially exposed to BSE-tainted beef products (Table 6-1).

U.S. military members and their families who were living in the United Kingdom and Europe between 1980 and 1996 were at increased risk of exposure to infectious prions as a result of their consumption of locally procured beef or their consumption of beef in local eating establishments compared with the risk of their counterparts in the United States. This risk of acquiring vCJD is judged to have been relatively small compared with the local population's risk. Notification and active prospective surveillance are not warranted for these military members or their families. However, the committee encourages passive

monitoring of the incidence of Creutzfeldt-Jakob disease (CJD) among military personnel.

Blood transfusions could also place deployed forces at risk of infection by the agent of BSE or of other transmissible spongiform encephalopathies (TSEs). In a situation in which a deployed service member is wounded or otherwise injured and needs a blood transfusion, where does that blood come from and what is the likelihood that it contains a TSE agent such as the infectious prion that causes vCJD?

DOD's blood supply is under the management of the Armed Services Blood Program (ASBP). The collection, processing, tracking, storage, and distribution of blood are closely managed (DOD, 1996). The majority of blood used by U.S. forces is collected at 24 blood collection sites: 18 sites in the United States and 6 sites overseas (Sparks, 2002). More than 90 percent of the blood collected at these sites comes from active-duty service members (Sparks, 2002). Some of the military's blood is frozen for longer-term storage and use. This stockpile was collected in the early 1990s, before the current blood donation deferral policy was in place (Personal communication, LTC

R.D.Sylvester, Armed Services Blood Program, November 5, 2002), and would be used only in a major military contingency situation in which fresh blood was unavailable.

The U.S. military deploys its own health care system in support of U.S. forces deployed overseas. That system includes medical providers, fixed and mobile hospitals, and medical supplies, including blood. In general, any blood given to a deployed service member would be collected and controlled by ASBP. Thus, the potential risk that a service member would be transfused with blood from a donor who might have preclinical vCJD is considered quite remote.

Under some circumstances, blood products are supplied to U.S. facilities by the host nation. Examples of such blood products include platelets, which have a very short shelf life, and products whose supplies are exhausted or not available. Additionally, U.S. forces deployed overseas use local emergency rooms or hospitals when medical care is not available from the DOD health care system. In situations in which the U.S. service member has an injury serious enough to warrant a blood transfusion, there would be a theoretical risk of exposure to an infectious prion such as that which causes vCJD, but those situations are uncommon.

Although the risk that a member of the deployed forces acquired a prion responsible for TSE from a blood transfusion is presumed to be very low, individuals who were deployed to Europe during the period of risk are not able to donate blood, according to DOD policy (Sparks, 2002). The Food and Drug Administration (FDA) and the American Red Cross have similar blood donation deferral policies (Table 6-2).

This policy results in the deferral of 18 percent of the DOD donors and has placed a significant burden on DOD's ability to maintain its blood supply. However, special recruiters at blood donor sites have increased collections 9 percent, which has helped to offset the losses (Sparks, 2002).

If a screening blood test that was sensitive enough to detect infectious prions were available, it might be possible to return to the blood donor pool more than 4 million donors whose DOD service in Europe precludes them from donating blood. In addition, approximately half a million non-DOD individuals (5 percent of the national blood donor pool) who are deferred from donating blood could be returned to the blood donor pool (Sparks, 2002).

The need to return individuals to the blood donor pool is driving the blood-servicing industry to make a screening test available. However, scientific evidence showing that blood from one person with CJD or vCJD can transmit the infectious agent by blood or blood product transfusion is lacking. A recent attempt to infect mice with the buffy coat and plasma of blood from a vCJD patient produced negative results (Bruce et al., 2001). However, this lack of evidence may result from inadequate knowledge of the behavior of prions in human blood,

the detection limits of today's prion detection assays, the limitations of cross-species bioassays, and the long incubation period of vCJD.

Of special concern was the finding that vCJD is present in lymphoid organs. The recent report of the successful transmission of the agents of BSE and scrapie between sheep by blood transfusion (Hunter et al., 2002) buttressed the precautions already in place to protect the public from the potential blood-borne transmission of vCJD. In addition, PrP^Sc (the protease-resistant protein associated with prion disease) was detected in the blood of a patient with sporadic Creutzfeldt-Jakob disease (sCJD) (Aguzzi, 2002). These reports magnify the importance of determining the amount of PrP^Sc in the blood of both sCJD and vCJD patients. The titer of infectious prions present should also be determined by assays with appropriate host species. This will require improved methods for detection of PrP^Sc and suitable hosts for transmission studies.

Ethical considerations and the present inability to identify presymptomatic carriers with vCJD or sCJD preclude the conduct of experiments to determine precisely whether the blood in those carriers is infectious for other humans. Therefore, scientists must rely on animal studies to estimate both the amount of PrP^Sc corresponding to one ID₅₀ (the dose needed to infect 50 percent of the population exposed to the agent) of vCJD or sCJD prions in human blood and the titer of those infectious proteins. Nonhuman primates are excellent animal models for these experiments. The National Prion Research Program of DOD should fund the infrastructure and research protocols for primate studies to determine both the amount of PrP^Sc corresponding to one ID₅₀ of vCJD and sCJD prions in human blood and the titers of those infectious proteins in human blood.

Until circulating PrP^Sc in blood can be detected with confidence, blood donation deferral policies must be based on worst-case assumptions, namely, that persons who are known to have been exposed to infectious prions and who are possibly incubating them should be deferred from the blood donor pool.

This chapter has summarized the risks that deployed U.S. forces have of acquiring a TSE as a result of the consumption of a contaminated food product or the receipt of a tainted therapeutic blood product. Both risks are deemed small to nonexistent. Nevertheless, the risk is unknown, so the precaution of deferring individuals who were potentially exposed to BSE-contaminated meat from donating blood is justified. Research that can clarify the infectious potential of blood products as a vehicle for transmitting prions will help immensely.

Aguzzi A. 2002. Unresolved problems in prion science. Presentation to the IOM Committee on Transmissible Spongiform Encephalopathies, Meeting II. The National Academies, Washington, D.C.

Bruce ME, McConnell I, Will RG, Ironside JW. 2001. Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues. Lancet 358(9277):208-209.

DoD (U.S. Department of Defense). 1996. Department of Defense Instruction 6480.4. Washington, D.C.: Armed Services Blood Program, U.S. Department of Defense.

DoD. 2001. Active duty military personnel strengths by regional area and by country. Department of Defense Almanac. [Online]. Available: http://www.defenselink.mil/pubs/almanac/aknanac/people/serve.html [accessed October 20, 2002].

Hunter N, Foster J, Chong A, McCutcheon S, Parnham D, Eaton S, MacKenzie C, Houston F. 2002. Transmission of prion diseases by blood transfusion. Journal of General Virology 83(Pt 11):2897-2905

Severin SR. 2002. Protecting the DoD food supply from TSEs. Presentation to the IOM Committee on Transmissible Spongiform Encephalopathies: Assessment of Relevant Science, Meeting I . The National Academies, Washington, D.C.

Sparks RA. 2002. Armed Services Blood Program vCJD update. Presentation to the IOM Committee on Transmissible Spongiform Encephalopathies: Assessment of Relevant Science, Meeting I. The National Academies, Washington, D.C.