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Transfusion-Associated Transmission of West Nile Virus --- Arizona, 2004

Blood transfusion--associated transmission (TAT) of West Nile virus (WNV) in the United States was first identified in 2002 (1). In 2003, blood collection agencies (BCAs) responded by screening donations for WNV by using nucleic acid--amplification tests (NATs) (2). The majority of BCAs use a two-tiered NAT-screening algorithm. On the basis of the test manufacturer's format, NATs are conducted on minipools of samples from either six or 16 blood donations. If a minipool is nonreactive, its constituent donations are released for transfusion. If a minipool is reactive, the constituent donations undergo individual testing. If an individual donation is reactive, associated blood components are impounded, and the donor is notified for further testing to confirm the infection. In 2003, blood-donation screening for WNV resulted in the impounding of approximately 800 blood components potentially containing WNV. However, six reported cases of transfusion-associated WNV disease were associated with units of blood components with viral concentrations too small to be detected by minipool NAT (3). In 2004, to improve the sensitivity of WNV screening, BCAs implemented systems to trigger a switch from minipool NAT to individual NAT in areas with epidemic WNV transmission. This report describes the first transfusion-associated WNV infection identified in 2004; the implicated blood donation was collected before the switch to individual testing. Clinicians should remain aware of the risk for WNV transmission through blood-product transfusion and alert state health officials to hospitalized patients with WNV disease symptoms who have had a transfusion during the preceding 28 days.

Case Report

In July 2004, a man aged 43 years was admitted to a tertiary-care hospital in Maricopa County, Arizona, for an above-knee amputation necessitated by complications of diabetes mellitus. The patient was anemic and received two units of packed red blood cells (RBCs). His surgery occurred 3 days after admission, and he was discharged in stable condition 8 days later.

Two days after discharge, after a day of malaise, anorexia, and diarrhea, the man was found unresponsive and was admitted to a local hospital. On admission, his wound site was clean, but he was hypoglycemic and had an erythematous maculopapular rash on his upper extremities. He remained poorly responsive despite treatment for hypoglycemia, and the next day he was transferred to the tertiary-care hospital that had performed his amputation. On admission, he was febrile, had altered mental status, oscillopsia, and cogwheel rigidity. Magnetic resonance imaging of the brain was consistent with WNV encephalitis (4). The patient's cerebrospinal fluid was positive for WNV-specific IgM antibody by enzyme-linked immunosorbent assay at the Arizona Bureau of State Laboratory Services and positive for WNV RNA by reverse transcriptase--polymerase chain reaction at CDC.

The patient was discharged to a nursing home in mid-August and died 3 days later. Primary cause of death was cardiorespiratory failure secondary to severe progressive neurologic dysfunction. An autopsy was not performed.

The RBC units the patient received were produced from two donations collected in June in Maricopa County. Both donations were nonreactive by minipool NAT screening. Two fresh frozen plasma units associated with these donations were recalled and tested individually for WNV. One plasma unit was nonreactive by NAT, and a follow-up sample from the donor was negative for WNV IgM. The other plasma unit was reactive by NAT, but negative for WNV-specific IgM antibody. To determine the efficacy of minipool testing for this unit, a minipool including this plasma unit was reconstructed and was reactive in two of 10 replicated minipool NAT tests. Individual NAT was reactive in nine of 10 replicated tests. Follow-up donor serum was positive for WNV IgM.

Because the transfusion recipient had a confirmed WNV infection, the implicated donation was NAT reactive, and the associated donor seroconverted; this is considered a probable case of WNV TAT (3). As of July 27, only one WNV-infected horse and no human cases of WNV disease had been reported in the recipient's county of residence. However, this case does not meet the criteria for a confirmed case of WNV TAT because the patient traveled to an area experiencing epidemic WNV transmission for his amputation. Exposure of the patient to infectious mosquitoes while in this area cannot be ruled out.

Reported by: S Caglioti, Blood Systems Laboratories, Tempe; P Tomasulo, MD, Blood Systems Incorporated, Scottsdale; R Raschke, MD, M Rodarte, DO, Banner Good Samaritan Medical Center, Phoenix; T Sylvester, A Diggs, MPH, Maricopa County Dept of Public Health; C Kioski, MPH, C Levy, MS, Arizona Dept of Health Svcs. M Traeger, MD, J Redd, MD, J Cheek, MD, Indian Health Svc. M Kuehnert, MD, Div of Viral and Rickettsial Diseases; S Montgomery, DVM, Div of Bacterial and Mycotic Diseases; A Marfin, MD, R Lanciotti, PhD, G Campbell, MD, T Smith, MD, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases; J Brown, DVM, EIS Officer, CDC.

Editorial Note:

As of September 7, a total of 98 blood components potentially containing WNV had been removed from the U.S. blood supply during 2004. The risk for WNV transmission via blood products has been reduced but not eliminated. Minipool NAT is an effective screening method for WNV, but donations containing low levels of virus can escape detection by this test. Although individual NAT is more sensitive than minipool NAT, the United States has limited laboratory capacity and test reagent availability for NAT. For this reason, BCAs developed systems to trigger a switch from minipool to individual NAT in areas of epidemic WNV transmission (5). Nonetheless, in the case described in this report, results of testing the implicated donation revealed that even individual NAT might not have detected WNV (i.e., in one of 10 tests).

BCAs in the United States had not planned to implement their trigger systems until June 2004. However, the WNV epidemic in Maricopa County began in May, earlier than widespread WNV was expected. Evidence of year-round WNV activity has been documented in east Texas and Louisiana (6). This year's experience demonstrates that BCAs might need to prepare for onset of human WNV transmission as early as May in areas of the country similar to Arizona. As a result of the case described in this report, the BCA involved plans to implement its trigger system year-round in all its collection areas.

Clinicians should consider WNV disease in any patient with consistent symptoms who has received a blood transfusion during the 28 days preceding illness onset. Suspected cases should be reported to state health authorities, who are encouraged to notify CDC. The vigilance of clinicians and public health officials is essential to identify breakthrough TAT cases. Identification of such cases allows recovery of stored components that might contain WNV, which further increases the safety of the blood supply.

The benefits of blood transfusion far outweigh the risk for transfusion-associated WNV disease. However, clinicians should use blood products judiciously to reduce the risk for adverse events and should be alert for cases of transfusion-associated WNV disease. BCAs will continue to evaluate WNV-screening strategies in consultation with CDC and the Food and Drug Administration to ensure that blood products are as safe as possible.


This report is based, in part, on contributions by A Lambert, A Noga, MPH, R Hochbein, D Martin, N Crall, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC.


  1. 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--45.
  2. CDC. Detection of West Nile virus in blood donations---United States, 2003. MMWR 2003;52:769--72.
  3. CDC. Update: West Nile virus screening of blood donations and transfusion-associated transmission---United States, 2003. MMWR 2004;53:281--4.
  4. Solomon T. Flavivirus encephalitis [Review]. N Engl J Med 2004;351: 370--8.
  5. Custer B, Tomasulo PA, Murphy EL, et al. Triggers for switching from mini-pool nucleic acid technology testing to individual donation testing: analysis of 2003 data to inform 2004 decision-making. Transfusion 2004 (in press).
  6. Tesh RB, Parsons R, Siirin M, et al. Year-round West Nile virus activity, Gulf Coast region, Texas and Louisiana. Emerg Infect Dis 2004;10:1649--52.

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