WNV in Blood (6): Transmission & Testing 2004

TRANSFUSION-ASSOCIATED TRANSMISSION OF WNV -- ARIZONA, 2004

Source: CDC MMWR Weekly September 17, 2004 / 53(36);842-844 [Full Text]
        <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5336a4.htm>

Blood transfusion-associated transmission (TAT) of WNV in the US 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 US 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.

Acknowledgments

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.
References

    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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Received on Thu Sep 23 12:47:34 2004