Detection of West Nile Virus in Blood Donations --- United States, 2003

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During the 2002 epidemic of West Nile virus (WNV) in the United States, a total of 23 persons were reported to have acquired WNV infection after receipt of blood components from 16 WNV-viremic blood donors (1), and an estimated 500 viremic donations might have been collected (B. Biggerstaff, M.D., CDC, personal communication, 2003). Because of the possibility of recurrent WNV epidemics in the United States, blood collection agencies (BCAs) recently implemented WNV nucleic acid--amplification tests (NATs) to screen all donations and quarantine and retrieve potentially infectious blood components. In addition to NAT screening, the Food and Drug Administration (FDA) recommended that BCAs enhance donor deferral questions by specifically asking about fever with headache occurring in the week before donation and defer persons reporting such symptoms (2). This report describes the NAT screening process for two WNV-viremic donors and presents data summarizing the testing results for approximately 95% of the civilian blood donations collected during late June to early August. These preliminary data suggest that investigational screening tests are effective in identifying viremic donations and preventing the implicated blood components from entering the blood supply.

Screening Procedures

Two commercial WNV-screening NATs have been distributed under phase III investigational new drug (IND) approval by FDA. The Roche assay is based on a real-time, quantitative reverse transcriptase polymerase chain reaction (PCR) format (Taqman^®), and the GenProbe-Chiron assay is based on a transcription-mediated amplification format. Both assays identify highly conserved regions of the WNV genome. Depending on the test format, aliquots of the donation are combined with aliquots from other donors into pools of six (Roche assay) or 16 (GenProbe-Chiron assay) for NAT. If the pool is NAT- reactive, the individual samples that had been combined are tested separately by using the same NAT-screening format. Some laboratories test individual donations with no pooling. When an individual donation is NAT-reactive, all blood components associated with that donation are quarantined; unused components from any donation given by the same donor within the preceding 14--28 days are retrieved. As part of the test evaluation under the investigational status, a series of additional NATs are performed on alternate samples from the implicated donation (i.e., an aliquot from the donated plasma). Additional amplification testing is usually performed by a second laboratory using a different amplification format or primers that are reactive with a different part of the WNV genome. The original donation sample and blood samples collected after the donation are assayed for WNV-specific IgM antibody to document seroconversion in the donor. Donor information, including recent travel history, other exposure history, and review of symptoms compatible with WNV illness before or after donation, is collected by questionnaire within 14 days of donation.

To assist with national WNV surveillance and control efforts, BCAs share WNV NAT-screening data with state health departments. Full confirmatory testing under the IND protocols might not be completed in time to serve public health needs; therefore, preliminary screening results are reported to the state health department of the donor's state of residence. Donors are presumed to be WNV viremic when samples from the initial donation are reactive in the screening NATs of the pool, reactive using the screening NAT as individual samples, and repeatedly reactive as individual samples using an additional NAT. The American Association of Blood Banks, CDC, and FDA collaborated to request BCAs to report the state of residence, age, sex, postal code, and date of donation of presumptive viremic donors (3).

Examples of NAT Screening Process

Donor 1. On June 25, 2003, a resident of Harris County, Texas, aged 47 years donated blood locally. A pool of six samples, including this donation, was reactive on NAT screening performed the same day. When individual donations were tested, this person's donation was the only reactive donation identified from the initially reactive pool. A sample of the plasma component (i.e., alternate sample) was tested on June 26 by using the same NAT format and was found to be reactive. On June 27, the BCA reported this case to the Harris County Public Health and Environmental Services as a presumptive WNV infection. Subsequent PCR testing using alternate primers and NAT formats at three different laboratories, including CDC, confirmed the presence of WNV RNA in the blood with an estimated viral load of 7,200 copies/mL (18 plaque-forming units [pfu]/mL). Plasma samples collected from this donor by the BCA 14 and 28 days post-donation did not contain WNV RNA; serologic testing is pending. The donor reported no symptoms suggestive of WNV illness either before donation or during the 4 weeks post-donation. On July 2, the NAT manufacturer reported having sequenced an amplicon (i.e., the amplified segment of viral genome generated by PCR) that was homologous with the 1999 New York strain of WNV. At CDC, WNV was isolated from the plasma. This donor would be eligible to donate blood again 28 days after the original donation (i.e., the most recent reactive NAT result) according to the IND protocol.

Donor 2. On July 9, a South Dakota resident aged 24 years donated blood locally. On July 10, initial screening of the pool of six samples was NAT-reactive. Testing of the individual donor's sample also was reactive on this date, and the BCA notified the South Dakota Department of Health. Aliquots of the donated plasma were tested by using alternate WNV primers and NAT formats at a second laboratory, the South Dakota Public Department of Health State Laboratory, and CDC; all tests were reactive. The viral load was estimated to be 160,000 copies/mL (400 pfu/mL). WNV-specific antibody was identified in a sample collected 14 days post-donation; the donor reported fever and malaise from the second day to the fourth day post-donation.

Status of Blood Donation Screening for WNV

Of the approximately one million donations screened as of August 5, a total of 329 (approximately 0.03%) were found reactive for WNV infection by using the NAT format. Of these 329 donations, 163 (approximately 0.015% of total donations) were repeatedly reactive when tested with an additional NAT; results of additional NATs for 28 screening test--reactive donations are pending. The more than one million donations screened represent approximately 95% of the blood collected in the United States during that period; however, testing was performed on all donations. As of August 5, state health departments have reported 38 presumptive WNV-viremic donors to ArboNET, the cooperative surveillance project between CDC and 57 state and local health departments. These presumptive WNV-viremic donors have been reported from Colorado, Florida, Louisiana, Mississippi, New Mexico, South Dakota, and Texas. The remaining donors identified by the BCA community have yet to be reported to public health officials in the donors' states of residence or have not yet been reported to ArboNET by public health departments.

Reported by: SL Stramer, PhD, American Red Cross, Gaithersburg, Maryland. S Caglioti, Blood Systems Laboratories, Tempe, Arizona. DM Strong, PhD, Puget Sound Blood Center, Seattle, Washington. K Sazama, MD, Anderson Cancer Center, Houston, Texas. W Dickey, MD, Bonfils Blood Center, Denver, Colorado. S Kleinman, MD, American Association of Blood Banks, Victoria, British Columbia, Canada. H Nakhasi, J Epstein, J Goodman, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. MJ Kuehnert, MD, Div of Viral and Rickettsial Diseases; A Marfin, MD, N Crall, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases; S Montgomery, DVM, EIS Officer, CDC.

Editorial Note:

On the basis of information gathered from BCAs, the investigational screening tests currently in use are successfully identifying viremic donations and preventing the implicated blood components from entering the blood supply. Follow-up testing and data collection performed by BCAs on all presumptive viremic donors identified by the initial screening tests is necessary to confirm these infections, but identification of probable infections might be valuable to surveillance efforts at the state level.

The WNV-screening NAT was commercially developed and implemented during a 9-month period, from September 2002, when the need was identified, to the initiation of donation testing in June 2003. As of July 14, all civilian blood donations collected in the United States, including Puerto Rico, have been screened for WNV by using NATs.

WNV nucleic-acid detection was identified as the most efficient means of interdicting viremic donations, as opposed to donor deferral on the basis of donor symptoms or serologic testing. In addition, since 1999, all blood donations have been screened for human immunodeficiency virus--1 and hepatitis C virus by virus detection using NAT-based methods in a pooled screening format. As a result, testing infrastructure and familiarity with these methods and formats were in place at regional blood screening laboratories. Although the technology for NAT of sample pools will probably detect the majority of viremic donations, the sensitivity of testing in field settings is still under investigation. As a result, patients who have received blood transfusions within 4 weeks preceding the development of febrile illness compatible with WNV infection should be reported to CDC through the local public health authorities to initiate an investigation.

WNV viremia in humans typically lasts an average of 6 days (4,5) and is thought to peak shortly before or within a few days of the onset of symptoms among persons who have WNV illness (6). After illness onset, the concentration of virus in the bloodstream decreases, and detectable amounts of WNV-specific IgM antibody increase. During the investigations of clinical illness resulting from transfusion of WNV-infectious blood products in 2002, the implicated donors were estimated to have had viremia as low as 0.8 pfu/mL, and many were asymptomatic in the week before or after donation. In all cases in which transfusion transmission of WNV infection was proven, the donated blood was negative for IgM. However, the possibility of transfusion transmission from donors with detectable IgM concurrent with low-level viremia has not been excluded.

After the issuance of industry-wide guidelines from the American Association of Blood Banks (3), which allow for protection of blood donor confidentiality, reporting to public health officials of presumed positive donors has been performed voluntarily by blood banks in several states. The current investigational screening tests are designed to be sensitive for the initial testing of pooled samples from as many as 16 donors. Because of the high sensitivity of these tests, public health officials should be cautious in the use of preliminary test result data because false-positive results can occur. As part of the protocols for evaluation of these investigational tests, all blood products from a donation found to be WNV-reactive on initial individual donation screening are excluded from the blood supply. Because the majority of WNV-infected persons remain asymptomatic, collection of data about viremic donors might serve as an essential surveillance tool in addition to screening for removal of potentially infectious products from the blood supply. State health departments receiving reports of these donors are encouraged to notify CDC through ArboNET as part of the national surveillance of human WNV infection.

This report is based on contributions by S Rossmann, MD, Gulf Coast Regional Blood Bank, Houston, Texas. L Kightlinger, PhD, South Dakota Dept of Public Health. R Dodd, PhD, American Red Cross, Rockville, Maryland. BG Bartley, MSc, Armed Svcs Blood Program Office, Falls Church, Virginia. RS Lanciotti, PhD, JT Roehrig, PhD, GL Campbell, MD, LR Petersen, MD, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC.

References

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