Vaccines, Blood & Biologics
Draft Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
- I. Introduction
- II. Background
- III. Recommendations for Testing Donors of HCT/Ps
- IV. Implementation
- V. References
- About this guidance document
- How to comment on this document
- To obtain copies of this document
- For questions regarding this document
- FDA office that authored this guidance
I . Introduction
We, FDA, are providing you, establishments that make donor eligibility determinations for donors of HCT/Ps, with recommendations for donor testing for West Nile Virus (WNV) using an FDA-licensed donor screening test. We believe that the use of an FDA-licensed nucleic acid test (NAT) will reduce the risk of transmission of WNV from donors of HCT/Ps and therefore recommend that you use an FDA-licensed NAT for testing donors of HCT/Ps for infection with WNV. This guidance provides information and recommendations regarding NAT testing of HCT/P donors for WNV. This draft guidance replaces the draft guidance entitled “Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)” dated April 2008 (April 28, 2008, 73 FR 22958) with respect to HCT/Ps. The testing recommendations in this guidance, when finalized, will supplement the donor screening recommendations for WNV (which will remain in place) that were made in the guidance entitled “Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)” dated August 2007 (2007 Donor Eligibility Guidance) (Ref. 1), in section IV.E. recommendations 15 and 16, section IV. F. recommendation 5, and Appendix 6 (and supersede the discussion of testing in Appendix 6).
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA’s guidances means that something is suggested or recommended, but not required.
A. Regulatory Background
In 2002, test manufacturers and blood organizations, with input from Public Health Service representatives (National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and FDA) actively pursued development of NAT systems for WNV. A workshop entitled “Development of Donor Screening Assays for West Nile Virus” was held on November 4-5, 2002 (Ref. 2). The workshop discussed the possibility that WNV would be recognized as a relevant communicable disease agent or disease for HCT/Ps when appropriate screening tests were developed. Also, FDA, during its presentation, discussed the need for FDA-approved tests to detect WNV in cadaveric blood samples.
Since 2002, studies have documented human-to-human transmission of WNV by blood transfusion and by organ transplantation (Refs. 3, 4).
As discussed in the 2007 Donor Eligibility Guidance, FDA determined WNV to be a relevant communicable disease agent or disease in accordance with 21 CFR 1271.3(r)(2). This determination was based on the severity of the effects of WNV, its incidence and prevalence in the donor population, the potential for transmission of WNV by HCT/Ps, and the availability of appropriate screening measures. The 2007 Donor Eligibility Guidance contained specific recommendations for donor screening for WNV but not for donor testing.
Under the regulations, establishments must perform donor testing to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents and diseases, unless one of the few exceptions apply (21 CFR 1271.80(a), 1271.85(a), 1271.90). An establishment may determine a donor to be eligible only if the results of donor testing are negative or nonreactive (21 CFR 1271.50(b)(2)). However, in 2007, we did not recommend testing of HCT/P donors for WNV, in recognition of the limited availability of such tests. We stated in the 2007 Donor Eligibility Guidance that we may recommend routine use of an appropriate, licensed donor screening test(s) to detect acute infections with WNV using NAT technology, once such tests were available (Ref. 1).
In April 2008, we published a draft guidance entitled “Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)” dated April 2008 (April 28, 2008, 73 FR 22958) (Ref. 5). The following year, we finalized the recommendations in that guidance for donations of Whole Blood and blood components, in the guidance entitled “Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion” dated November 2009 (November 9, 2009, 74 FR 57685) (Ref. 6). In the notice of availability that announced the finalized guidance, we stated that we were continuing to review public comments submitted on our recommendations for testing HCT/P donor specimens for WNV. In the notice, we also expressed our intention to seek additional public input and to issue guidance for testing HCT/P donor specimens for WNV in the future.
In July 2010, the American Association of Tissue Banks (AATB) hosted a public workshop entitled, “West Nile Virus Workshop: Scientific Considerations for Tissue Donors.” Workshop participants included subject-matter experts from AATB-accredited tissue banks (including reproductive tissue banks), Eye Bank Association of America (EBAA) representing accredited eye banks, FDA, CDC, the United States Department of Health and Human Services (HHS), Health Canada, the Public Health Agency of Canada, and other stakeholders. The goal of the workshop was to develop public interest in relevant scientific studies to fill the gaps in the knowledge of WNV in human tissues. The data generated by such studies could further inform regulatory decisions regarding HCT/P donor screening and testing for WNV (Ref. 7).
B. WNV Epidemiology and Public Health Impact
WNV is an arthropod-borne virus (arbovirus) which has a single-stranded ribonucleic acid (RNA) in the family Flaviviridae. WNV was first detected in the United States (U.S.) in 1999, during an outbreak in the New York City area (Ref. 8). WNV has become endemic with high viral activity during the warm months of the year. WNV is maintained in nature primarily in a mosquito-bird-mosquito transmission cycle involving Culex (Cx.) species mosquitoes (Cx. pipiens, Cx. tarsalis, and Cx. quinquefasciatus), but can also infect other animals, such as birds and horses (Ref. 9). Humans can also be infected with WNV (Refs. 9, 10).
Birds are the natural reservoir hosts for WNV. Many WNV-infected avian species develop transient viremia sufficient to infect feeding mosquitoes (Ref. 11). Birds commonly survive their infections and develop permanent immunity, although certain species become ill and die (Ref. 12). Humans are considered dead-end hosts for the virus since they do not develop viremia sufficient to allow virus transmission to feeding mosquitoes (Ref. 13).
Approximately 80% of WNV infections in humans result in an asymptomatic infection. The clinical features of WNV infections in the 20% of humans who are symptomatic are broad-ranging and vary from febrile illness that includes headache, myalgia, arthralgia, rash, or gastrointestinal symptoms (Refs. 14, 15) to the development of neuroinvasive disease, which occurs in less than 1% of infected humans. West Nile Neuroinvasive Disease (WNND), which typically presents as a panencephalitis, meningitis, or acute flaccid paralysis (AFP), may lead to irreversible neurological damage, coma, and death (Refs. 15, 16, 17). WNV is the leading cause of neuroinvasive arboviral disease in the U.S. The average annual incidence of WNND in the U.S. was 0.4 per 100,000 population from 1999 to 2008, with a peak in 2002 (see table 1 for the WNND annual incidence rates from 2002-2011) (Refs. 18 through 22). Risk factors for development of WNND include: male sex; being over the age of 50; diabetes; and being immunocompromised (Refs. 20, 21, 22).
Table 1. West Nile Neuroinvasive Disease Annual Incidence in the U.S. a
WNND No. of
Annual incidence WNND
a See http://www.cdc.gov/ncidod/dvbid/westnile/index.htm for more details.
C. Transfusion-transmitted WNV Infection
The potential for WNV transmission by blood transfusion was first recognized in 2002. WNV transmission usually occurs during the acute phase of infection, when infected individuals are viremic and asymptomatic (Ref. 23). Few infected donors develop clinically significant disease. Studies have shown that questioning blood donors for recent illness suggestive of WNV infection is ineffective at identifying infected/seropositive donors (Refs. 24, 25). During 2002, CDC conducted investigations of five blood transfusion recipients who subsequently developed neurologic disease. In four of these five cases, there was WNV-associated disease in the blood recipients, including one fatality. In the fifth of the five transfusion cases, there was an unspecified encephalopathy in a recipient of a WNV TaqMan-positive blood product, but there was no documentation of seroconversion in this recipient (Ref. 26).
Pealer et al. reported a total of 23 confirmed cases of WNV transmission by blood and blood components in 2002, including the 5 above mentioned investigations reported by CDC. Of the 23 confirmed cases, 10 (43%) of the patients were immunocompromised due to immune suppression related to transplantation or cancer, and 8 (35%) were older than 70 years of age. All 23 infected recipients were linked to 16 donors with evidence of viremia at the time of donation. In follow-up studies with the donors, 9 of the 16 donors reported viral symptoms before or after donation, five were asymptomatic, and two were lost to follow-up. All 16 donors were immunoglobulin M (IgM) seronegative at the time of donation (Ref. 3).
The cases in 2002 involving transfusion-transmitted WNV infection prompted the initiation of donor testing by 2003. In June 2003, blood establishments began to screen blood donations for WNV by NAT using two different tests under FDA’s Investigational New Drug Application (IND) regulations (21 CFR Part 312). The protocols implemented to screen donations included minipool NAT (MP-NAT) testing of samples using minipools of either 6 or 16 donations, depending on the manufacturer, followed by individual testing (ID-NAT) of each donation that was part of any reactive minipool (Ref. 17). Between July 1 to October 31, 2003, blood donor testing at American Red Cross (ARC) and participating members of America’s Blood Centers (ABC) yielded 944 confirmed viremic donors out of 4,585,573 units screened (1 in 4,858 donations). The average length of time viremia was detectable by MP-NAT was 6.9 days (Ref. 25). The data from ARC and ABC indicates that approximately 1,000 West Nile viremic donors in the U.S. were identified between July 1st and October 31st in 2003, by prospective NAT screening, and that therefore, about 1,500 potentially infectious blood components were identified and interdicted before transfusion (Ref. 25).
In addition, in 2003, a total of 36 suspected cases of WNV transfusion-transmitted infections were reported to CDC. Upon investigation, of the 36 cases, five were classified as probable cases and one was classified as a confirmed case. In each of these six cases, the recipients received blood components from multiple donations; however, only one infectious blood component was found in each case. All six infectious donations had been collected between July 29, 2003 and September 18, 2003, and had not been detected by MP-NAT (Ref. 27).
Until 2004, all WNV testing in blood donors was performed using MP-NAT. Late in 2004, there was a transition from MP-NAT testing to ID-NAT in geographic regions with high WNV activity during epidemic periods. While there were 15 suspected cases of transfusion-transmitted WNV infections investigated in 2004, only one probable transfusion-transmitted case was documented. The WNV transmission resulted from a blood donation which tested nonreactive in a MP-NAT assay. In 2005, there were eight suspected cases investigated, and there was no documented transfusion-transmitted WNV infection (Ref. 27).
Since the implementation of routine screening of blood products for WNV, transfusion-associated WNV infections have been rare (Refs. 6, 28). Since implementation of screening in 2003, 12 transfusion-associated transmissions of WNV have been documented, according to the CDC (Ref. 28). Most recently, CDC reported a case of fatal WNV encephalitis in a severely immunosuppressed patient after probable transfusion-associated transmission. The subsequent investigation suggested that the implicated donation contained a level of viral load that was near the limit of detection of the NAT assays used for the screening, and therefore produced inconsistent results on repeated testing (Ref. 28).
In 2006, transfusion-transmitted WNV infection occurred in two immunocompromised individuals who experienced onset of WNND after receiving blood products from a single infected donor, despite a negative MP-NAT result at the time of donation (Ref. 29). In October 2008, the Louisiana Department of Health (LDH) reported two cases of probable transfusion-transmitted WNV infections from a common blood donor. One infection resulted in WNND via organ donation from an organ donor who had received blood from a WNV-infected blood donor. The other case resulted in asymptomatic WNV infection directly to the blood transfusion recipient (Ref. 30).
D. Transplant-transmitted WNV Infection
- WNV transmission via solid organ transplantation
WNV is not just transmissible via blood transfusion, but also is transmissible via organ transplantation. Although organ donors are not routinely tested for WNV (Ref. 29), multiple WNV transmissions via organ transplantation have been reported in published medical literature. For example, in 2002, a published report from CDC identified four solid organ transplantation recipients that developed WNV infection. Three of the four recipients developed WNND, and one recipient died. The attributed mortality rate is therefore 25% (Ref. 4). Additionally, since 2002, there have been 14 reported cases of WNV infections transmitted to recipients by solid organ transplantation. In three recipients from a single donor who had a febrile illness prior to fatal head injury, retrospective testing of stored donor blood samples were reactive for WNV IgM, but not for WNV RNA by NAT testing (Ref. 30). In the remaining 11 cases, there was a probable or confirmed transmission via organ transplantation. Of these 14 cases, three (21%) were asymptomatic, one (7%) developed a febrile illness, one (7%) was found to be viremic and nine (64%) developed WNND. Of those nine individuals who developed WNND, one (11%) resulted in death, three (33%) resulted in coma, two (22%) had severe motor or cognitive permanent damage, two (22%) recovered, and one has an unknown outcome (Refs. 4, 29, 30, 31, 32, 33).
- WNV transmission via HCT/P transplantation
The potential for WNV transmission through hematopoietic progenitor cell (HPC) is presumably similar to that of blood transfusion-given the similarities in the product composition and donor characteristics (e.g., recovered from similar populations composed of healthy, living donors). Unlike the majority of recipients of blood, however, typical recipients of HPCs are severely immunocompromised, and are more likely to experience serious outcomes as a result of WNV infection. Therefore, the risk of WNV transmission is a particularly important consideration for this patient population. In 2003, there was a published report of two cases of WNND in patients receiving HPC for the treatment of acute myeloid leukemia. In one of these patients the source of the WNV was not determined, and in the other the WNV was traced to a blood transfusion (Ref. 34). More recently, there is a published report of WNV transmission as a result of a granulocyte transfusion to a patient with persistent neutropenia related to cancer chemotherapy (Ref. 35). In this case, although the donor was tested for WNV, the limited shelf life of the granulocyte necessitated transfusion of the patient with the granulocyte apheresis product prior to obtaining results of the WNV testing.
Scientific data on the risk of transmission of WNV through transplantation of other HCT/Ps are limited and uncertain. The paucity of reports of WNV transmission via transplantation of other cell and tissue products may reflect factors such as differences in viral load between tissues, and the potential for decreased transmissibility due to viral inactivation procedures specific to some of these products. Additionally, asymptomatic or mild non-specific symptoms of WNV infection in healthy recipients may go unnoticed in the setting of concomitant treatments making attribution to a transplanted HCT/P challenging. We recognize the potential usefulness of future studies to better understand the rate of transmission in HCT/P donation, and to ascertain clinical performance characteristics of donor screening assays when used on specimens collected from cadaveric (non-heart-beating/post-asystole) HCT/P donors.
E. Assay Development and Performance
Nationwide clinical studies to evaluate NAT for the detection of WNV were initiated in 2003, under FDA’s IND regulations. Such large-scale studies were undertaken to help ensure blood safety and to determine the efficacy of investigational blood assays to prevent the transmission of WNV through blood transfusion, because, at that time, there was no FDA-licensed screening assay available to detect WNV infection. Donors of HPCs were also tested in this initiative as part of the IND studies.
Since 2005, FDA has approved biologics license applications (BLAs) for NAT assays for detecting WNV RNA in plasma specimens from donors of blood and blood components, and blood specimens from donors of organs and tissues. Two assays that are licensed for testing specimens from donors of Whole Blood and blood components are also licensed for testing both living and cadaveric (non-heart-beating/post-asystole) HCT/P donors. These assays are intended for use in testing individual donor specimen from such donors. In addition, these assays may also be used for testing pools of human plasma in “minipools” comprised of equal aliquots of individual donations from volunteer donors of whole blood and blood components.
ID-NAT may identify additional reactive donations not detected by MP-NAT, as WNV generally has a low viral load (median 3,519 copies/mL, range < 50 to 690,159) (Ref. 36), and when the viral load is near the assay limit of detection, there may be erratic test results (Ref. 37). Retrospective studies using ID-NAT to test specimens that had been MP-NAT nonreactive identified additional reactive donations. Up to 25% of viremic units were not detected by MP-NAT, presumably due to low viral load (Ref. 38). Thus, these studies show that ID-NAT has greater sensitivity than MP-NAT for detecting WNV. Moreover, data have shown that up to 10% of blood donors who have a reactive ID-NAT that fails to be reactive on repeat testing by ID-NAT actually are infected, based on the presence of antibodies to WNV either in the index donation (approximately 8%) or on a follow-up test (approximately 2%) (Ref. 38). Therefore, there is no presumption that an initial positive WNV ID-NAT that is not reactive on repeat testing is a false positive result.
As noted above and as described at greater length in the 2007 Donor Eligiblity Guidance, WNV is a relevant communicable disease agent or disease as defined in 21 CFR 1271.3(r)(2). We now determine that testing for WNV is necessary to adequately and appropriately reduce the risk of transmission of WNV. Therefore, FDA recommends that:
- HCT/P donors should be tested for WNV by ID-NAT using a licensed NAT donor screening test.
- Any HCT/P donor whose specimen tests negative (or non-reactive) for WNV by ID-NAT should be considered to be negative (or non-reactive) for WNV for purposes of determining donor eligibility.1
Any HCT/P donor whose specimen tests positive (or reactive) for WNV must be considered ineligible to donate (21 CFR 1271.50(b)(2), 1271.80(d)(1)).
We recommend that you implement this guidance within six months after the final guidance is issued. The guidance will apply to HCT/Ps recovered from donors on or after the final guidance issue date.
- Food and Drug Administration, Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (August 2007) http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/ucm073964.htm.
- Food and Drug Administration, Workshop on Development of Donor Screening Assays for West Nile Virus (November 4, 2002) http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/TranscriptsMinutes/UCM054461.pdf.
- Pealer LN, et al., Transmission of West Nile Virus through Blood Transfusion in the United States in 2002. N Engl J Med. 349:1236-45 (2003).
- Iwamoto M, et al., Transmission of West Nile Virus from an Organ Donor to Four Transplant Recipients. N Engl J Med. 348, 2196-2203 (2003).
- Food and Drug Administration, Draft Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (April 2008).
- Food and Drug Administration, Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion (November 2009). http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM189464.pdf.
- Brubaker SA, Rigney P. West Nile Virus Workshop: Scientific Considerations for Tissue Donors. Cell Tissue Bank . 2012 ; 499-511
- Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile Virus Infection in the New York City Area in 1999. N Engl J Med 2001;344:1807-14.
- Hayes CG. West Nile fever. In: Monath TP, ed. The arboviruses: epidemiology and ecology, Vol V. Boca Raton, FL: CRC Press, 1989;59-88.
- Turell MJ, Dohm DJ, Sardelis MR, Oguinn ML, Andreadis TG, Blow JA. An Update on the Potential of North American Mosquitoes (Diptera: Culicidae) to Transmit West Nile Virus. J Med Entomol 2005;42:57-62.
- Work TH, Hurlbut HS, Taylor RM. Indigenous Wild Birds of the Nile Delta As Potential West Nile Virus Circulating Reservoirs. Am J Trop Med Hyg 1955;4:872-88.
- Komar N, Panella NA, Burns JE, Dusza SW, Mascarenhas TM, Talbot TO. Serologic Evidence for West Nile Virus Infection in Birds in the New York City Vicinity During an Outbreak in 1999. Emerg Infect Dis 2001;7:621-25.
- Hayes EB, Komar N, Nasci RS, Montgomery SP, O'Leary DR, Campbell GL. Epidemiology and Transmission Dynamics of West Nile Virus Disease. Emerg Infect Dis 2005;11:1167-73.
- Mostashari F, Bunning ML, Kitsutani PT, Singer DA, Nash D, Cooper MJ, Katz N, Liljebjelke KA, Biggerstaff BJ, Fine AD, Layton MC, Mullin SM, Johnson AJ, Martin DA, Hayes EB, Campbell GL. Epidemic West Nile Encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet 2001; 358:261-64.
- Davis LE, DeBiasi R, Goade DE, Haaland KY, Harrington JA, Harnar JB, Pergam SA, King MK, DeMasters BK, and Tyler KL. West Nile Virus Neuroinvasive Disease. Ann Neurol 2006:60:286-300.
- Sejvar JJ, Marfin AA. Manifestations of West Nile Neuroinvasive Disease. Rev Med Virol 2006; 16:209-224.
- MMWR 2004 Centers for Disease Control and Prevention. Update: West Nile Virus Screening of Blood Donations and Transfusion –Associated Transmission ---United States, 2003. 2004 MMWR 53(13): 281-284.
- MMWR 2010 Centers for Disease Control and Prevention. Surveillance for Human West Nile Virus Disease- United States, 1999-2008. 2010 MMWR 59 (SS02): 1-17.
- MMWR 2011 Centers for Disease Control and Prevention. West Nile Virus Disease and Other Arboviral Diseases- United States, 2010. 2011 MMWR 60(30): 1009-1013.
- MMWR 2012 Centers for Disease Control and Prevention. West Nile Virus Disease and Other Arboviral Diseases - United States, 2011. 2012 MMWR 61(27): 510-514.
- World Health Organization Media Centre West Nile Virus. Fact Sheet N 354, July 2011, http://www.who.int/mediacentre/factsheets/fs354/en/index.html.
- Jean CM, Honarmand S, Louie JK, Glaser CA. Risk Factors for West Nile Virus Neuroinvasive Disease, California, 2005. Emerg Infect Dis 2007;13:1918-20.
- Biggerstaff BJ, Petersen LR. Estimated Risk of West Nile Virus Transmission Through Blood Transfusion During an Epidemic in Queens, New York City. Transfusion. 42:1019-26 (2002).
- Custer B, Kamel H, Kiely NE, Murphy EL, Busch MP. Associations Between West Nile Virus Infection and Symptoms Reported by Blood Donors Identified Through Nucleic Acid Test Screening. Transfusion. 2009 Feb;49(2):278-88.
- Busch MP, Wright DJ, Custer B, Tobler LH, Stramer SL, Kleinman SH, Prince HE, Bianco C, Foster G, Petersen LR, Nemo G, Glynn SA. West Nile Virus Infections Projected From Blood Donor Screening Data, United States, 2003. Emerg Infect Dis. 2006 Mar;12(3):395-402.
- MMWR 2002 Centers for Disease Control and Prevention. Investigations of West Nile Virus Infections in Recipients of Organ Transplantation and Blood Transfusion. 2002 MMWR 51(37): 833-836.
- Montgomery SP, Brown JA, Kuehnert M, Smith TL, Crall N, Lanciotti RS, Macedo de Oliveira A, Boo T, Marfin AA; 2003 West Nile Virus Transfusion-Associated Transmission Investigation Team. Transfusion-Associated Transmission of West Nile Virus, United States 2003 through 2005. Transfusion. 2006 Dec;46(12):2038-46.
- MMWR 2012 Centers for Disease Control and Prevention. Fatal West Nile Virus Infection After Probable Transfusion-Associated Transmission- Colorado, 2012. 62(31): 622-624
- MMWR 2009 Centers for Disease Control and Prevention. West Nile Transmission Via Organ Transplantation and Blood Transfusion-- Louisiana, 2008. 2009 MMWR 58(45): 1263-7.
- MMWR 2005 Centers for Disease Control and Prevention. West Nile Virus Infections in Organ Transplant Recipients---New York and Pennsylvania, August—September 2005. 2005 MMWR 54(40): 1021-3.
- Morelli MC, Sambri V, Grazi GL, Gaibani P, Pierro A, Cescon M, Ercolani G, Cavrini F, Rossini G, Capobianchi MR, Di Caro A, Menzo S, Pagliaro PP, Ghinelli F, Lazzarotto T, Landini MP, Pinna AD. Absence of Neuroinvasive Disease in a Liver Transplant Recipient Who Acquired West Nile Virus (WNV) Infection from the Organ Donor and Who Received WNV Antibodies Prophylactically. Clin Infect Dis 2010 Aug 15;51(4):e34-7.
- Inojosa WO, Scotton PG, Fuser R, Giobbia M, Paolin A, Maresca MC, Brunello A, E. Nascimben E, Sorbara C, Rigoli R Berti R, Gajo GB, Giometto B. West Nile Virus Transmission Through Organ Transplantation in North-Eastern Italy: A Case Report and Implications for Pre-Procurement Screening. Infection. Published online; 29 April 2012. DOI 10.1007/s15010-012-0263-4.
- Cushing MM, Brat DJ, Mosunjac MI, Hennigar RA, Jernigan DB, Lanciotti R, Petersen LR, Goldsmith C, Rollin PE, Shieh WJ, Guarner J, Zaki SR. Fatal West Nile virus encephalitis in a renal transplant recipient. Am J Clin Pathol. 2004 Jan;121(1):26-31.
- Hong DS, Jacobson KL, Raad II, de Lima M, Anderlini P, Fuller GN, Ippoliti C, Cool RM, Leeds NE, Narvios A, Han XY, Padula A, Champlin RE, Hosing C. West Nile encephalitis in 2 hematopoietic stem cell transplant recipients: case series and literature review. Clin Infect Dis 2003;37:1044-49.
- Meny GM, Santos-Zabala L, Szallasi A, and Stramer SL. West Nile virus infection transmitted by granulocyte transfusion. Blood 2011; 117:5778-79.
- Busch MP, Caglioti S, Robertson EF, McAuley JD, Tobler LH, Kamel H, Linnen JM, Shyamala V, Tomasulo P, Kleinman SH. Screening the Blood Supply for West Nile Virus RNA by Nucleic Acid Amplification Testing N Engl J Med 2005; 353:460-467.
- Rios M, Daniel S, Dayton AI, Wood O, Hewlett IK, Epstein JS, Caglioti S, Stramer SL. In Vitro Evaluation of the Protective Role of Human Antibodies to West Nile Virus (WNV) Produced During Natural WNV Infection. J Infect Dis. 2008 Nov 1;198(9):1300-8.
- Stramer SL, et al., West Nile Virus Among Blood Donors in the United States, 2003 and 2004. N Engl J Med 2005; 353:451-59.
1. FDA’s recommendations regarding donor screening for WNV can be found in sections IV.E. and IV.F. of the 2007 Donor Eligibility Guidance (Ref. 1). Consistent with this guidance, persons who have tested positive or reactive for WNV infection using an FDA-licensed or investigational WNV NAT donor screening test in the preceding 120 days should be considered ineligible.
This draft guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the appropriate FDA staff. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
Submit one set of either electronic or written comments on this draft guidance by the date provided in the Federal Register notice announcing the availability of the draft guidance. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You should identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register.
Additional copies of this guidance are available from the Office of Communication, Outreach and Development (OCOD), (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or e-mail firstname.lastname@example.org, or from the Internet at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
For questions on the content of this guidance, contact OCOD at the phone numbers or e-mail address listed above.
U.S. Department of Health and Human Services
Food and Drug Administration
- Center for Biologics Evaluation and Research