Problem Solved? West Nile Virus and Transfusion Safety
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《新英格兰医药杂志》
In 2002, just three years after its appearance in the Western Hemisphere, West Nile virus caused the largest outbreak of arboviral encephalitis ever recorded in the United States.1 Epidemiologic investigations that year revealed that West Nile virus could be transmitted by blood transfusion,2 and mathematical models suggested that hundreds of transmissions had occurred.3 By July 2003, shortly before a second seasonal outbreak of similar magnitude began, collaborations among blood-collection organizations, test-kit manufacturers, and government agencies culminated in near-universal screening of U.S. blood donations for West Nile virus with the use of newly developed nucleic acid amplification tests.
In this issue of the Journal, two reports, one by Stramer et al.4 and one by Busch et al.,5 analyze the results of screening 7.1 million donations for West Nile virus, providing the first large-scale evaluation of the program. Initially, screening for West Nile virus was performed only on pooled blood samples from 16 donors ("minipools"). As expected, screening yields were characterized by extreme geographic and temporal variations. Remarkably, viremia was documented in as many as 1 in 150 donors in some areas during epidemics. From among approximately 27.2 million donations screened nationwide during the first two years of screening, from July 2003 through June 2005, 1039 blood donors with viremia were reported nationwide to the Centers for Disease Control and Prevention — a yield of 1 in 26,200. This yield compares with yields ranging from approximately 1 in 100 to 1 in 1000 donations for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) when screening for those viruses began.
Both Busch et al. and Stramer et al. confirm that the viremia associated with West Nile virus infection is of low titer and borders on the lower limit of sensitivity of the screening tests that use minipools. Of concern, approximately one third to one half of the donations with demonstrable viremia on nucleic acid amplification testing when evaluated individually were not identified by minipool screening, establishing that testing of individual donations had a substantially greater yield than minipool testing in areas with outbreaks. On this basis, individual donations were tested in various regions according to the regional rate of detection of West Nile virus by minipool screening.
However, the true benefits of testing individual donations may be more limited than it first appears. Both groups found that 8 to 15 percent of all donations with demonstrable viremia only on testing of individual donations lacked IgM antibody. Notably, all 30 cases of transfusion-transmitted West Nile virus that were documented from 2002 to 2004 resulted from IgM antibody–negative donations.2,6,7 Conversely, limited retrospective studies showed that transfused viremic donations missed by minipool screening did not transmit West Nile virus if IgM antibody was present. Further studies are needed to resolve whether IgM-positive donations are ever infectious. However, if we assume that the presence of IgM antibody prevents virus transmission and that nearly all viremic donations reported from July 2003 to June 2005 were based on detection by minipool screening, we estimate that minipool screening alone identified 93 percent of infectious donations, for a residual risk of less than 1 in 350,000, calculated according to the following formula: [(1039 ÷ 0.93) – 1039] ÷ 27.2 million. This risk can be compared with contemporary risks of transfusion-transmitted HBV of 1 in 220,000 donations, transfusion-transmitted HCV of 1 in 1,600,000 donations, and transfusion-transmitted HIV of 1 in 1,800,000 donations.8
The screening program for West Nile virus differs substantially in concept from those for HBV, HCV, and HIV. Although the risk of transfusion-transmitted HBV, HCV, and HIV derives mostly from a prolonged carrier state in donor populations with a relatively low and stable incidence of infection, the risk associated with West Nile virus derives mostly from a short, asymptomatic period of viremia in populations with an extremely variable and seasonal incidence of infection.3 Because the future incidence of West Nile virus infections is unknown, the long-term public health benefit of screening blood donations for this virus cannot yet be defined. A second difference is that serologic testing forms the cornerstone of screening for HBV, HCV, and HIV, whereas nucleic acid amplification testing for HCV and HIV eliminates a small, residual risk of transfusion-transmitted infection from incident infections.9 The high level of viremia typical of acute HCV and HIV infections translates into a very high level of sensitivity of nucleic acid amplification testing with minipools of up to 24 samples. In contrast, screening for West Nile virus relies solely on nucleic acid amplification testing of samples that often have very low viral titers.
The strong working relationships developed and expanded between public health officials and blood-collection agencies since the HIV epidemic in the early 1980s facilitated investigations of the first cases of possible transfusion-transmitted West Nile virus infection. Moreover, recent technological developments, such as screening for HIV and HCV with the use of nucleic acid amplification tests, allowed the rapid development and implementation of screening tests for West Nile virus. Subsequently, the screening program for West Nile virus forged a new rapid-response relationship between transfusion medicine and public health. Because the identification of donors with West Nile virus viremia may provide the earliest indication of mosquito-borne transmission to humans in a community, blood-collection agencies now notify health departments of these donors so that other control efforts can be heightened. For example, in 2004, viremic blood donors were identified first in 7 of the 57 counties in which both viremic blood donors and other human illnesses from West Nile virus were identified.
Our experience with West Nile virus tells us that the next emerging infectious-disease threat to the U.S. blood supply is probably one not yet imagined. Nevertheless, with the right collaboration of scientific disciplines and the adaptation of newer forms of technology, our ability to respond has never been better.
Source Information
From the National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colo. (L.R.P.); and the Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Md. (J.S.E.).
References
O'Leary DR, Marfin AA, Montgomery SP, et al. The epidemic of West Nile virus in the United States, 2002. Vector Borne Zoonotic Dis 2004;4:61-70.
Pealer LN, Marfin AA, Petersen LR, et al. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med 2003;349:1236-1245.
Biggerstaff BJ, Petersen LR. Estimated risk of transmission of the West Nile virus through blood transfusion in the US, 2002. Transfusion 2003;43:1007-1017.
Stramer SL, Fang CT, Foster GA, Wagner AG, Brodsky JP, Dodd RY. West Nile virus among blood donors in the United States, 2003 and 2004. N Engl J Med 2005;353:451-459.
Busch MP, Caglioti S, Robertson EF, et al. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. N Engl J Med 2005;353:460-467.
Update: West Nile virus screening of blood donations and transfusion-associated transmission -- United States, 2003. MMWR Morb Mortal Wkly Rep 2004;53:281-284.
Transfusion-associated transmission of West Nile virus -- Arizona, 2004. MMWR Morb Mortal Wkly Rep 2004;53:842-844.
Busch MP, Kleinman SH, Nemo GJ. Current and emerging infectious risks of blood transfusions. JAMA 2003;289:959-962.
Stramer SL, Glynn SA, Kleinman SH, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 2004;351:760-768.(Lyle R. Petersen, M.D., M)
In this issue of the Journal, two reports, one by Stramer et al.4 and one by Busch et al.,5 analyze the results of screening 7.1 million donations for West Nile virus, providing the first large-scale evaluation of the program. Initially, screening for West Nile virus was performed only on pooled blood samples from 16 donors ("minipools"). As expected, screening yields were characterized by extreme geographic and temporal variations. Remarkably, viremia was documented in as many as 1 in 150 donors in some areas during epidemics. From among approximately 27.2 million donations screened nationwide during the first two years of screening, from July 2003 through June 2005, 1039 blood donors with viremia were reported nationwide to the Centers for Disease Control and Prevention — a yield of 1 in 26,200. This yield compares with yields ranging from approximately 1 in 100 to 1 in 1000 donations for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) when screening for those viruses began.
Both Busch et al. and Stramer et al. confirm that the viremia associated with West Nile virus infection is of low titer and borders on the lower limit of sensitivity of the screening tests that use minipools. Of concern, approximately one third to one half of the donations with demonstrable viremia on nucleic acid amplification testing when evaluated individually were not identified by minipool screening, establishing that testing of individual donations had a substantially greater yield than minipool testing in areas with outbreaks. On this basis, individual donations were tested in various regions according to the regional rate of detection of West Nile virus by minipool screening.
However, the true benefits of testing individual donations may be more limited than it first appears. Both groups found that 8 to 15 percent of all donations with demonstrable viremia only on testing of individual donations lacked IgM antibody. Notably, all 30 cases of transfusion-transmitted West Nile virus that were documented from 2002 to 2004 resulted from IgM antibody–negative donations.2,6,7 Conversely, limited retrospective studies showed that transfused viremic donations missed by minipool screening did not transmit West Nile virus if IgM antibody was present. Further studies are needed to resolve whether IgM-positive donations are ever infectious. However, if we assume that the presence of IgM antibody prevents virus transmission and that nearly all viremic donations reported from July 2003 to June 2005 were based on detection by minipool screening, we estimate that minipool screening alone identified 93 percent of infectious donations, for a residual risk of less than 1 in 350,000, calculated according to the following formula: [(1039 ÷ 0.93) – 1039] ÷ 27.2 million. This risk can be compared with contemporary risks of transfusion-transmitted HBV of 1 in 220,000 donations, transfusion-transmitted HCV of 1 in 1,600,000 donations, and transfusion-transmitted HIV of 1 in 1,800,000 donations.8
The screening program for West Nile virus differs substantially in concept from those for HBV, HCV, and HIV. Although the risk of transfusion-transmitted HBV, HCV, and HIV derives mostly from a prolonged carrier state in donor populations with a relatively low and stable incidence of infection, the risk associated with West Nile virus derives mostly from a short, asymptomatic period of viremia in populations with an extremely variable and seasonal incidence of infection.3 Because the future incidence of West Nile virus infections is unknown, the long-term public health benefit of screening blood donations for this virus cannot yet be defined. A second difference is that serologic testing forms the cornerstone of screening for HBV, HCV, and HIV, whereas nucleic acid amplification testing for HCV and HIV eliminates a small, residual risk of transfusion-transmitted infection from incident infections.9 The high level of viremia typical of acute HCV and HIV infections translates into a very high level of sensitivity of nucleic acid amplification testing with minipools of up to 24 samples. In contrast, screening for West Nile virus relies solely on nucleic acid amplification testing of samples that often have very low viral titers.
The strong working relationships developed and expanded between public health officials and blood-collection agencies since the HIV epidemic in the early 1980s facilitated investigations of the first cases of possible transfusion-transmitted West Nile virus infection. Moreover, recent technological developments, such as screening for HIV and HCV with the use of nucleic acid amplification tests, allowed the rapid development and implementation of screening tests for West Nile virus. Subsequently, the screening program for West Nile virus forged a new rapid-response relationship between transfusion medicine and public health. Because the identification of donors with West Nile virus viremia may provide the earliest indication of mosquito-borne transmission to humans in a community, blood-collection agencies now notify health departments of these donors so that other control efforts can be heightened. For example, in 2004, viremic blood donors were identified first in 7 of the 57 counties in which both viremic blood donors and other human illnesses from West Nile virus were identified.
Our experience with West Nile virus tells us that the next emerging infectious-disease threat to the U.S. blood supply is probably one not yet imagined. Nevertheless, with the right collaboration of scientific disciplines and the adaptation of newer forms of technology, our ability to respond has never been better.
Source Information
From the National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colo. (L.R.P.); and the Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Md. (J.S.E.).
References
O'Leary DR, Marfin AA, Montgomery SP, et al. The epidemic of West Nile virus in the United States, 2002. Vector Borne Zoonotic Dis 2004;4:61-70.
Pealer LN, Marfin AA, Petersen LR, et al. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med 2003;349:1236-1245.
Biggerstaff BJ, Petersen LR. Estimated risk of transmission of the West Nile virus through blood transfusion in the US, 2002. Transfusion 2003;43:1007-1017.
Stramer SL, Fang CT, Foster GA, Wagner AG, Brodsky JP, Dodd RY. West Nile virus among blood donors in the United States, 2003 and 2004. N Engl J Med 2005;353:451-459.
Busch MP, Caglioti S, Robertson EF, et al. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. N Engl J Med 2005;353:460-467.
Update: West Nile virus screening of blood donations and transfusion-associated transmission -- United States, 2003. MMWR Morb Mortal Wkly Rep 2004;53:281-284.
Transfusion-associated transmission of West Nile virus -- Arizona, 2004. MMWR Morb Mortal Wkly Rep 2004;53:842-844.
Busch MP, Kleinman SH, Nemo GJ. Current and emerging infectious risks of blood transfusions. JAMA 2003;289:959-962.
Stramer SL, Glynn SA, Kleinman SH, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 2004;351:760-768.(Lyle R. Petersen, M.D., M)