Screening for West Nile Virus in Organ Transplantation: A
The Organ Procurement and Transplant Network (OPTN) has recently announced that screening for West Nile Virus (WNV) in deceased organ donors is not recommended at this time. The purpose of this report was to examine the impact of this recommendation by using medical decision analysis.

Without screening the rate of disease transmission was assumed to be the same as in donated blood with a case fatality rate of 25%. With screening we assumed the baseline screening test specificity and sensitivity to be 99.5% and 95%, respectively. The analysis was confined to heart, liver and kidney recipients. Survival probabilities and transplant rates were taken from UNOS.

Annual screening could result in the loss of potentially 452.4 life years (113.8 for heart, 272.6 for liver and 66.0 for kidney). Most positive test results would be false-positive. Screening would be preferable for kidney donors in areas of high disease prevalence and high test specificity. However, for heart and liver most scenarios were associated with a net loss of life with screening, except if patients were stable on the wait list with particularly high case fatality rates from WNV.

Current recommendations by OPTN that screening is not mandatory seem appropriate until further data are available.

West Nile Virus (WNV) is a mosquito-borne, single-stranded RNA flavivirus, which was first identified in 1937 but introduced to North America in 1999. Since then human infection has been reported in most states and in many provinces of Canada. The transmission season is long, with cases occurring into December in some parts of the United States. The virus has a longer history in Europe, Africa, Asia and the Middle East. Although the mosquito is the vector of disease transmission, human disease has also been acquired through blood transfusion, breast-feeding, transplacental transmission, occupational exposure in laboratory workers and stem cell and solid organ transplantation.

Most infections are mild, however, people older than 50 years with chronic medical conditions and those receiving immunosuppression are at highest risk of severe disease, which may include encephalomyelitis and death. Approximately 200 Americans were believed to have died from WNV in 2002. Case fatality rates are low among the general population but ranges between 4 and 29% for hospitalized patients. In the solid organ transplant recipient the case fatality rate is quite high. The limited number of documented cases and the lack of routine post transplant screening in all patients preclude an accurate estimation of this rate. Currently, there is no specific drug treatment or vaccine against the infection.

With respect to the transplant recipient, the most likely mode of transmission is also the mosquito. Preventive strategies, such as avoiding outside activities at dawn and dusk, using N,N-diethyl-m-toluamide (DEET)-containing repellents and eliminating breeding sites, will help reduce mosquito bite transmission. Routine blood-donor screening should reduce this mode of transmission. However there is as yet no endorsed strategy to test deceased organ donors in North America. The difficulty is detecting the infected potential donor. By the time serologic tests are positive the diseased individuals may no longer be infective, and the tests for detecting virus are time consuming, cross react with other viruses and may not detect low-level viremia.

The Organ Procurement and Transplantation Network (OPTN) and the Health Resources and Services Administration (HRSA) recently released their recommendations on the role of deceased donor screening in January 2004. They recommended that donors with encephalitis, meningitis or flaccid paralysis in geographic areas with human WNV infection be deferred. They acknowledged that some centers were testing deceased donors and added that organs with known reactive tests before transplantation be used only if the recipients were informed of the risk and had an emergent life-threatening illness requiring transplantation and no suitable alternative therapy. Because of testing logistics, the lack of a FDA-approved test and known limitations of testing with false-positive and -negatives, this group did not maintain that screening should be required at this time. Once a test is licensed, the organization recommends the appropriateness of screening be reassessed. Given the seriousness of this infection, delaying screening at this time may have a large negative impact on transplant outcomes. Quantifying the impact of screening would provide useful information to the transplant community.

The purpose of this report was to examine the impact of testing for WNV in deceased organ donors using a medical decision analysis model. This study examines the impact of lives lost or gained by introducing routine screening and examines the impact of test characteristics (sensitivity and specificity), specific solid-organ recipients (heart, liver and kidney), and the prevalence of the WNV-infected donor on these outcomes.