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
WNV RISK IN TRANSFUSION
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.
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
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).
SCREENING DONORS FOR WNV
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
Campbell GL et al. West Nile virus. Lancet Infect Dis 2002; 2:519-29.
Provisional Surveillance Summary – WNV Epidemic. MMWR 2002;
Biggerstaff et al. Estimated risk of West Nile virus transmission through
blood transfusion during an epidemic in Queens, NYC. Transfusion 2002;
West Nile virus and the blood supply: 2003. Blood Bulletin 2003; 6:1-2.
Couzin, J. Blood banks in a ‘Race against the mosquitoes’.
Science 2003; 299:1824.
©2003, Institute For Transfusion
Editor: Donald L. Kelley, M.D., MBA: