TMU Title Bar
Issue #4, 2003


West Nile Virus and Blood Transfusion


Lirong Qu, MD, PhD, Resident in Pathology
Darrell J. Triulzi, MD, Medical Director, The Institute for Transfusion Medicine



West Nile virus (WNV) was first isolated in 1937 from the blood of a febrile patient in the West Nile District of northern Uganda.  It is a mosquito-borne virus maintained in nature in a mosquito-bird-mosquito transmission cycle.  Humans and other mammals are incidental and dead-end hosts.  It is indigenous to Africa, Asia, Europe, and Australia.  Recent epidemics have occurred in Romania (1996), Russia (1999), and Israel (2000).1

After its first US appearance in New York City (1999), WNV completed its cross-continental trek in 2002.  Last year’s US outbreak was the largest reported West Nile meningoencephalitis (WNME) epidemic thus far, with 2,354 WNME cases among 3,389 reported WNV infections (as of Nov 30, 2002).2  The first documented cases of person-to-person WNV transmission through organ transplantation and blood transfusion, as well as, intrauterine infection via transplacental transmission, and a possible transmission through breastfeeding also appeared in 2002.2


West Nile Virus is a single-stranded RNA Flavivirus, serologically related to the agents of Japanese Encephalitis, St Louis encephalitis, Murray Valley encephalitis and the Kunjin virus (an Australian subtype of WNV).  The viral particle is approximately 50 nm in diameter with an 11 kb strand of RNA, which codes for three structural and seven non-structural proteins.  WNV has a lipid membrane embedded with the envelope proteins, the major structural protein serving as both a mediator for host-cell entry and a target for neutralizing antibodies.  The lipid envelope renders the virus susceptible to inactivation by detergents.


While most human WNV infections are asymptomatic, a minority (20%) present as a mild, flu-like illness with symptoms lasting from 3 to 6 days (“West Nile fever”).  Peak incidence occurs in late summer and the incubation period ranges from 3 to 14 days.  Less than 1% of infections result in severe neurological disease (WNME) with advanced age being the most significant risk factor for its development.3 

Information regarding the natural history of WNV infection in humans is based primarily on studies done in the 1950s.  Like many other viral infections, uncomplicated WN fever is a mild and common childhood disease in areas where WNV is endemic.  In some areas of Africa, the prevalence of immunity to WNV is about 50% in children and 90% in adults.  In these areas, epidemic WN fever and WNME are rare.1 

In contrast, immunity to WNV is virtually absent in the North American population.



In an immunocompetent host, WNV-specific antibodies (IgM followed by IgG) appear after infection, resulting in clearance of the virus from the circulation.  The viremic phase is estimated to last from 6 to 11 days, beginning about 2 days before the onset of illness. The virus is not known to persist in human hosts.  An IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) is used by local and state health departments to detect infection.3 In contrast to other transfusion-transmitted viruses (e.g. CMV, HIV), seropositivity is not indicative of WNV infectivity.  WNV IgM antibodies have been reported to persist for a year or more after initial infection.1



The risk of acquiring WNV infection through transfusion varies both seasonally and geographically.  In 1999, the estimated mean risk in Queens, New York City was 1.8 per 10,000 with a peak in late August and very low risk both before August and after September. 4  

For 2002, risk estimates increased to between 3 and 4 WNV infected donors per 10,000 with peak rates of up to 20 per 10,000 in severely affected areas.  Among the over 4,000 documented WNV cases in 2002, at least 21 WNV infections were transmitted via transfusion (14 donors). 5 

When compared to transfusion-transmitted hepatitis B, hepatitis C, or HIV, the risk of WNV is one to two orders of magnitude higher, making detection and exclusion of WNV infected donations from the blood supply a matter of high priority (even though a given individual has a far greater chance of becoming infected with WNV by a mosquito bite than through transfusion).



There is, currently, no FDA-approved donor screening test for WNV, so blood centers are placing greater emphasis on questioning and deferring donors for symptoms of illness, especially recent fever with headache, in order to limit WNV’s impact on the blood supply. 

At the urging of the Blood Products Advisory Committee of the FDA, manufacturers have been working diligently to develop a new WNV assay.  Because the magnitude of viremia seen in WNV infection tends to be low, the test being developed utilizes nucleic acid technology (NAT), molecular amplification of the viral genome, for enhanced sensitivity.6 This test, which will be implemented nationwide under a research IND protocol, is expected to be available by July 1, 2003.   

The implementation of NAT testing of the blood supply for hepatitis C and HIV has resulted in a reduction in transmission risk for those diseases to 1 in 1.5 – 2 million.5 Hopefully, NAT testing for WNV will have a similar impact.



Until the blood supply can be screened with the yet-to-be-released NAT test for WNV, the risk of transfusion-transmitted WNV must be included in decisions to transfuse, especially in non-urgent situations.  Accordingly, physicians should utilize the most current information on WNV risk, which is available from the CDC7 and from state health departments.8 Consents for transfusion should also reflect this risk. 

If the WNV risk is considered significant, physicians may opt to delay elective surgery and non-urgent medical transfusions or use autologous blood for transfusion when appropriate. 

For all transfusions, the risk of transfusion-transmitted disease (including that of WNV) must be weighed against the expected medical benefits of transfusion.  For medically necessary transfusions, the benefits will virtually always outweigh the risk of transfusion-transmitted WNV.5



  1. Campbell GL et al. West Nile virus. Lancet Infect   Dis 2002; 2:519-29.

  2. Provisional Surveillance Summary – WNV  Epidemic. MMWR 2002; 51:1129-33.


  4. Biggerstaff et al. Estimated risk of West Nile virus  transmission through blood transfusion during an epidemic in Queens, NYC. Transfusion 2002; 42:1019-26.

  5. West Nile virus and the blood supply: 2003. Blood Bulletin 2003; 6:1-2.

  6. Couzin, J. Blood banks in a ‘Race against the mosquitoes’.   Science 2003; 299:1824.



Copyright ©2003, Institute For Transfusion Medicine 

Editor: Donald L. Kelley, M.D., MBA:

For questions regarding this TMU, please contact Darrell J. Triulzi, MD at: (412) 209-7304.

Copies of previous Transfusion Medicine Update issues can be obtained from our web page:  To be placed on our mailing list for a hard copy, please contact Deborah Small by e-mail: or by phone: (412) 209-7320.