DHHS Eagle graphic
ASL Header
Mission Nav Button Division Nav Button Grants Nav Button Testimony Nav Button Other Links Nav Button ASL Home Nav Button
US Capitol Building
HHS Home
Contact Us
dot graphic Testimony bar

This is an archive page. The links are no longer being updated.

Testimony on Creutzfeldt-Jakob Disease (CJD) and the Blood Supply by David Satcher, M.D., Ph.D.
Director, Centers for Disease Control and Prevention
Public Health Service
U.S. Department of Health and Human Services

Before the House Committee on Government Reform and Oversight, Subcommittee on Human Resources
July 31, 1997

Good morning. I am Dr. David Satcher, Director of the Centers for Disease Control and Prevention (CDC). I am accompanied by Dr. Mary Chamberland, Dr. Bruce Evatt and Dr. Lawrence Schonberger with CDC's National Center for Infectious Diseases. We are pleased to be here this morning to discuss with you issues related to blood safety; specifically, the safety implications of plasma pool sizes and our surveillance efforts related to Creutzfeldt-Jakob Disease (CJD) and the blood supply.

As the report published nearly a year ago by this subcommittee found, the Nation's blood supply is safer than it has ever been. However, the blood supply continues to face infectious disease challenges from both recognized, as well as unknown threats. Ensuring that the Nation's supply of blood and blood products is free of infectious agents is a public health responsibility shared within the Department of Health and Human Services (HHS) by CDC, the Food and Drug Administration (FDA), and the National Institutes of Health (NIH). While CDC has no regulatory responsibility for blood safety, as the Nation's Prevention Agency, it has the expertise and responsibility for surveillance and detection of public health risks associated with receipt of blood and blood products. In collaboration with FDA, CDC also keeps the public informed concerning such risks.

Since I last addressed the subcommittee in November 1995 on this subject, CDC has implemented a number of steps to improve our ability to monitor and respond to potential threats to the blood supply in the United States. Blood safety is a priority area in CDC's strategy to prevent emerging and reemerging infectious diseases. CDC has enhanced several of its surveillance systems, including those that monitor infections in persons who have hemophilia. CDC has also developed new surveillance programs, such as the system to detect bacteria associated transfusion reactions that was described in a recent Morbidity and Mortality Weekly Report (MMWR). This past year, CDC, in collaboration with FDA, responded rapidly to conduct a number of epidemiologic and laboratory investigations, including bacterial sepsis associated with contamination of intravenous albumin and possible exposure to porcine parvovirus among persons receiving porcine factor VIII concentrate. CDC has also created a full-time position, occupied by Dr. Chamberland, to facilitate intra- and interagency coordination of CDC's blood safety activities. In addition, CDC continues to participate actively in the PHS Interagency Working Group on Blood Safety; the HHS Blood Safety Committee, the FDA Blood Products Advisory Committee and Transmissible Spongiform Encephalopathy Advisory Committee, and the newly formed HHS Advisory Committee on Blood Safety and Availability.

You have asked me to address two specific issues related to blood safety. The first is the relationship between plasma pool size and the risk of infectious diseases; the second is the effectiveness of surveillance efforts to detect CJD in the blood supply and the experimental work that suggests the potential for transmission of CJD through blood products.

Infectious Disease Risks Associated with Plasma Pool Size

The risks for infectious diseases associated with plasma products such as albumin, immunoglobulins, and clotting factor concentrates, have decreased dramatically since the introduction of donor screening and testing, and most importantly, effective virus inactivation procedures. Viruses, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are readily and efficiently inactivated by such procedures. Since implementation of these inactivation procedures beginning in the mid- 1980s, transmissions of HIV, HBV, and HCV by U.S. licensed products have been virtually eliminated in recipients of clotting factor concentrates. Prior to this, clotting factor concentrates carried a substantial risk of transmitting HBV and HCV infection; and most tragically, nearly 10,000 persons with hemophilia were infected with HIV in the early 1980s. Unfailing adherence to chemical and physical inactivation procedures and their further refinement, combined with donor screening, are our most critical safeguards for plasma products.

Despite screening and viral inactivation techniques, blood products made from plasma carry risks for transmission of other blood borne infectious agents. For example, clotting factor concentrates made from human plasma are still known to commonly transmit human parvovirus B 19 and, in rare instances, hepatitis A. These infections are extremely resistant to the viral inactivation practices used in current manufacturing processes. In addition, the potential exists for other, as yet unknown agents, to be transmitted if their infectivity cannot be eliminated through current inactivation practices. One strategy that has been proposed is to reduce or limit the number of individual donors who contribute to the large pools of plasma that are used in the manufacture of these products.

Typically, pients would be involved.

CDC believes that setting an upper limit on the number of individual donors who contribute to pools used in the manufacturing of plasma products would be beneficial. Smaller pool sizes would provide an increased margin of safety to persons who receive single or infrequent infusions of plasma products. In addition, an industry-wide standard would be established. FDA is in the best position to work with industry to define an upper limit and determine how it can be implemented most expeditiously. If production practices require a large volume, one approach would be for manufactures to create pools made from repeat donations. This would decrease the number of donors in a pool without reducing the volume of the pool and the amount of available product, even after quality control testing. Whatever strategies or manufacturing changes are initiated, it will be critical to ensure that our efforts to improve the safety of blood products do not result in interim product shorroducts automatically increases the risk for exposure to other infectious agents that are not inactivated. This is true for persons who receive a single or infrequent infusion (e.g., intramuscular immunoglobulin) -- a smaller pool size would reduce their risk of transmission of blood borne infections. In addition, use of smaller volume pools by manufacturers could result in less disruption of supplies of blood derivatives and less expense in the event lot(s) of product are recalled, since fewer recipients would be involved.

CDC believes that setting an upper limit on the number of individual donors who contribute to pools used in the manufacturing of plasma products would be beneficial. Smaller pool sizes would provide an increased margin of safety to persons who receive single or infrequent infusions of plasma products. In addition, an industry-wide standard would be established. FDA is in the best position to work with industry to define an upper limit and determine how it can be implemented most expeditiously. If production practices require a large volume, one approach would be for manufactures to create pools made from repeat donations. This would decrease the number of donors in a pool without reducing the volume of the pool and the amount of available product, even after quality control testing. Whatever strategies or manufacturing changes are initiated, it will be critical to ensure that our efforts to improve the safety of blood products do not result in interim product shortages.

Creutzfeldt-Jakob Disease

In January 1997, Dr. Lawrence Schonberger summarized for the subcommittee available epidemiologic information about the potential transmissibility of CJD by blood and blood products. I would like to review the major points of his testimony as well as reiterate CDC's assessment that the risk of transmission of CJD by blood and blood products is extremely small, if it exists at all.

CDC understands the concern of the subcommittee and others about the potential transmissibility of CJD by blood and blood products. CJD is an invariably fatal brain disease that is caused by an unconventional agent. Disinfection is unusually difficult. Incubation periods are long -- measured in years; and there is no practical screening test to identify those who are incubating the disease. In addition, since the 1970s, cases of CJD associated with medical procedures, such as those caused by infected pituitary-derived growth hormone and dura mater grafts, have been increasingly recognized.

The most direct reason for concern about the risk of transmitting CJD by blood products are laboratory and experimental studies. These studies have demonstrated the possible, occasional presence of the CJD agent in minimal amounts in the blood of infected patients and have demonstrated the infectivity of blood throughout most of the incubation period in two different rodent models of CJD. Studies also have demonstrated the infectivity of the buffy coat (i.e., that part of blood that contains white blood cells and platelets), the plasma, and some derivatives from plasma, particularly cryoprecipitate, when injected into the brains of animals. In at least one study, CJD was transmitted in an animal model by intravenous inoculation of blood from a sick animal. Some of these studies have been conducted by Dr. Paul Brown from the NIH.

How closely animal models mimic human CJD, particularly the infectivity of blood throughout most of the incubation period, is not known; nor can we directly infer from them the risk, if any, of transmission of CJD by transfusion of blood and blood products. To help answer these critical questions, it is necessary to focus on available epidemiologic data.

First, CDC is aware of no compelling evidence for any instance of transmission of CJD to a human recipient by blood or blood products. The absence of such case reports contrasts to what happened in the United States in the 1980s, when reports first appeared describing transmission of CJD by pituitary- derived growth hormone and by a commercial brand of dura mater grafts. Further, the recent report from the United Kingdom of the possible spread of Bovine Spongiform Encephalopathy (13 SE) to humans in the form of a new variant of CJD has increased physician and public awareness about CJD.

Second, case control studies are often the most practical epidemiologic studies for identifying risk factors for rare disease, such as CJD. The results of at least five such studies have consistently demonstrated that a history of a blood transfusion is not a risk factor for CJD. In none of these studies were patients with CJD more likely to have a history of blood transfusion than control subjects.

Third, CDC conducts routine surveillance for CJD through ongoing review of national mortality data. Results from 1979-1995 indicate that annual rates of CJD have remained stable (at about 1 case per million population). Thus, despite regular blood donation by persons who subsequently develop CJD, blood transfusions do not appear to be amplifying CJD infections in the U.S. population. None of the 3,905 reported cases of CJD was also reported to have hemophilia, thalassemia, or sickle cell disease -- diseases associated with increased exposure to blood or blood products, such as clotting factor concentrates and/or cryoprecipitate. Because many such patients are exposed to blood products at a very early age, it is noteworthy that no CJD cases were reported in persons 5-19 years of age in the United States during this 17 year period.

Fourth, CDC has undertaken to supplement its routine surveillance for CJD with an increased focus on persons with hemophilia. As part of this effort, CDC expanded its collaboration with hemophilia treatment centers beginning in October 1995 by: 1) active solicitation of more than 140 centers for any case reports of CJD; and 2) facilitating neuropathological examinations of brain tissue from deceased hemophilic patients with neurologic disorders to look for signs of CJD and the presence of the agent thought to cause the disease. Despite active solicitation of treatment centers, as well as efforts to increase providers' awareness about CJD through educational symposia at national hemophilia meetings, no center has reported a patient with clinical CJD. CDC continues to make follow-up inquiries to the largest of these centers. Suitable autopsy material from 30 persons with hemophilia has been received to date. Neuropathological examination has been completed for 26 of these persons; none had evidence of CJD.

Finally, to further enhance the evidence derived from routine surveillance, CDC is assisting the American Red Cross in coordinating a long-term, follow-up study of recipients who received blood components from donors who were subsequently reported to have been diagnosed with CJD. Using primarily the national death index through 1995, the vital status of 178 recipients of transfusable blood components from 14 donors who subsequently developed CJD was determined; none of these recipients were reported to have died of CJD. Among these recipients, 41 persons lived 5 or more years after their transfusion, including nine who lived as long as 13 to 24 years.

Data from two additional sources have demonstrated similar findings. First, the Puget Sound Blood Center and Program in Seattle has shared with CDC follow-up data from a cohort of 101 persons who each received more than 100 units of cryoprecipitate for a bleeding disorder between 1979 and 1985. Cryoprecipitate is the blood component that contained the highest titers of the CJD agent in the recently reported animal model experiments. It has been estimated that several thousand persons with hemophilia nationwide have been treated with at least some cryoprecipitate; however, the Puget Sound patients were treated primarily with cryoprecipitate. Of these 101 persons, 76 remain alive a minimum of 11 to 17 years after receipt of cryoprecipitate; none of the 25 persons who have died were reported to have developed CJD. The second study was done in Germany; none of 27 patients who definitely, or eight who probably, received a unit of blood from a CJD donor died of CJD. At least 13 of these patients survived 10 years or longer after the transfusion.

You have asked that I specifically address the effectiveness of our efforts to detect CJD that may be related to receipt of blood and blood products. CDC is aware of two studies which indicate that routine mortality surveillance has good sensitivity to detect CJD cases. The first study, conducted in 11 states, found that 80 percent of all neuropathologically confirmed cases of CJD during 1986-1988 could be ascertained by review of death certificates. The second study was conducted in early April 1996 in four Emerging Infections Program sites in three states and two metropolitan areas as part of active surveillance for the newly reported variant of CJD and physician-diagnosed cases of CJD. In these surveillance areas, greater than 90 percent of all pathologists, neurologists, and neuopathologists were contacted. Of the 94 CJD deaths identified during 1991-1995, 81 (86 percent) were found from death certificate review. These findings were reported in the CDC's MMWR on August 9, 1996.

Our efforts to supplement routine surveillance for CJD with focused activities in hemophilia treatment centers have met with varying success. The response to requests for reporting the number of patient deaths and patients who might have clinical CJD has been good. However, obtaining brain tissue from deceased hemophilia patients to examine for evidence of CJD has proved to be challenging. First, of the 140 Federally-funded hemophilia treatment centers that were invited to participate in this endeavor, only 52 volunteered. We attribute the modest level of participation to several reasons, including: 1) insufficient personnel and resources; 2) small size of some centers; 3) surveillance not being a routine function; and 4) CDC's direct funding of centers did not occur until October 1996, a year after initiation of the program in 1995. Second, we have received a small number of brain autopsy specimens, and most have been from persons who died before October 1995 when this program was initiated. According to records obtained from participating treatment centers, of 56 persons with bleeding disorders who died during January 1996-July 1997, 20 had central nervous system symptoms; of these 20, brain autopsy material from 6 (30 percent) persons has been identified to date. There appear to be a number of reasons for the small number of brain autopsies. Brain autopsy is not routinely performed on hemophilia decedents. Permission for an autopsy must be obtained during a time of family grief and high emotions. Hemophilia treatment staff have reported that it is difficult and uncomfortable to approach families of dying persons about consenting to a brain autopsy. A significant number of deaths occur outside of the hospital; consequently, hemophilia treatment center staff often become aware of these deaths after it is too late to obtain material for examination. Finally, there is a reluctance on the part of pathologists to perform brain autopsy on persons known to be infected with HIV and possibly CJD.

CDC has developed a number of approaches to help increase both the level of participation by hemophilia treatment centers and the number of brain autopsies performed on persons with hemophilia who die with neurologic disorders. In October 1996, CDC began direct funding of hemophilia treatment centers in order to implement a nationally coordinated prevention program to reduce or eliminate the complications of hemophilia. CDC is in the process of fostering changes in the hemophilia treatment centers which will provide a needed surveillance and communication network. This will facilitate a quicker response time for investigation of reports of possible transmission of blood borne agents. As part of this program, CDC is phasing in a nationwide monitoring system, the "Universal Data Collection System," which will collect information about the occurrence and severity of blood borne infections among persons with bleeding disorders, provide free testing for blood borne infections, and retain blood specimens to evaluate new agents that may threaten the safety of the blood supply. Implementation of the system, which has necessitated modification of many operating procedures in the 140 hemophilia treatment centers, is expected to be complete in 1998. When completely implemented, the system should capture nearly all blood borne infections occurring in patients treated at Federally-funded hemophilia treatment centers and improve participation in the CJD surveillance activities. Until then, CDC is working hard to improve awareness and participation in these activities.

We believe that educating patients and physicians on the importance of the neuropathological examination component, and encouraging patients to enroll before they become ill, will increase the number of autopsies. CDC plans to develop and distribute educational materials to hemophilia consumer and advocacy groups in addition to treatment centers regarding the CJD surveillance study. Additional efforts include working with pathologists to resolve concerns related to the handling of HIV- infected tissues and specimens and educating medical care providers about the importance of obtaining brain autopsies. Lastly, the implementation of the Universal Data Collection System may help recruitment for CJD surveillance. For example, the Universal Data Collection System informed consent process may facilitate discussions between care providers and patients about blood safety concerns, such as CJD, and lead to greater understanding and acceptance of the CJD surveillance project.


Ensuring the safety of the Nation's blood supply is an important public health priority and one to which CDC remains strongly committed to address. As part of its continued vigilance for emerging threats to the blood supply, CDC has a number of surveillance systems for the detection of diseases that may be transmitted in the blood supply. Surveillance is a critical component of CDC's mission. One of the four goals of CDC's strategic plan, "Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States," is the improvement and expansion of surveillance and response capabilities for infectious diseases in the United States and globally. Enhanced surveillance can play an important role in helping to ensure the safety of our blood and plasma products.

This morning, I have described CDC's surveillance and epidemiologic studies related to CJD and how we plan to strengthen these efforts. Surveillance and epidemiologic data have certain limitations and must be interpreted with caution. They cannot establish the absence of a risk. However, surveillance and epidemiologic data from both the United States and other countries provide increasing support for CDC's conclusion that, despite some experimental evidence suggesting a potential for blood borne transmission of CJD, the risk of transmission of CJD by blood products in humans is extremely small and remains theoretical. Periodic reevaluations of accumulating data will undoubtedly provide a stronger scientific basis for modifying, as appropriate, public health policies on CJD and blood safety in the future.

The current level of the safety of the blood supply largely reflects improvements in the areas of donor screening and education- serologic screening tests for viral pathogens; and viral inactivation techniques. The General Accounting Office, in its November 1996 report, Blood Supply: Transfusion-Associated Risks, indicated that new interventions will likely be of decreasing benefit and stated that new interventions will require careful consideration in order to identify areas of improvement that would maximize safety with reasonable costs. Limiting pool size is one intervention that could further improve the safety of blood products in some situations. However, compared to the aforementioned improvements that are already in place, the additional margin of safety to be gained is likely far less. We concur with the FDA's proposal that some upper limit on pool size be established. This would create a needed industry-wide standard. We urge that careful deliberation and study be undertaken by public health officials, industry, and consumers in advance of implementing pool size limitations to ensure that the supplies of these life-saving products are not jeopardized.

Thank you for the opportunity to testify before the Subcommittee. I will be happy to answer any questions you may have.

Privacy Notice (www.hhs.gov/Privacy.html) | FOIA (www.hhs.gov/foia/) | What's New (www.hhs.gov/about/index.html#topiclist) | FAQs (answers.hhs.gov) | Reading Room (www.hhs.gov/read/) | Site Info (www.hhs.gov/SiteMap.html)