West Nile virus in Canadian blood donors

BACKGROUND: Blood donation screening for West Nile virus (WNV) RNA by nucleic acid testing (NAT) was implemented in Canada in July 2003, and 14 WNV RNA-positive donations were identified. Samples were screened in minipools of six donations with a WNV assay (TaqScreen, Roche). Two of the donors were identified by single-donor screening that was initiated in the province of Saskatchewan, which had the highest prevalence of WNV in the country, in early September 2003. STUDY DESIGN AND METHODS: The original 14 samples and follow-up samples (2-35 days after donation), available from 13 of the 14 donors were tested with an in-house, real-time, quantitative WNV NAT assay that was specific for WNV. A Health Canada reference reagent was used for calibration. Immunoglobulin M (IgM) and immunoglobulin G (IgG) levels were determined with commercial enzyme-linked immunosorbent assay kits. RESULTS: All donors tested positive for the presence of WNV with the in-house assay. Two donors, 18 and 19, identified by single-donor testing, had extremely low levels of viremia and that could only be detected in 1:38 or 1:39 replicate tests. The titers of the remaining index samples ranged from below log2.8 (the limit of quantitation) to log4.7 NAT detectable units per mL. Three samples, from Donors 17, 18, and 19, were IgM-positive, whereas samples from Donors 18 and 19 were also IgG-positive. The remaining 10 donors with follow-up samples all seroconverted. CONCLUSION: The 14 WNV donor samples detected by routine screening were confirmed as WNV RNA-positive by a WNV RNA-specific in-house assay and by demonstration of seroconversion in 13 of the 14 donors.     

Associations between West Nile virus infection and symptoms reported by blood donors identified through nucleic acid test screening

BACKGROUND: Blood collected in the United States and Canada is screened for West Nile virus (WNV) using nucleic acid testing (NAT). The role that donor-reported symptoms of infection disclosed at or shortly after donation may play in enhancing blood safety has been debated. Little data are available on subsequent manifestations of WNV-specific disease outcomes in viremic donors.
STUDY DESIGN AND METHODS: Donors with initially reactive NAT results were informed by telephone and asked to complete symptom interviews. The questionnaires are focused on three time periods: the week before, the day of, and the 2 weeks after donation. Symptoms and risk factors were compared between confirmed-positive and false-positive donors (classified based on confirmatory NAT and serology). Additional analyses comparing confirmed-positive symptomatic and asymptomatic donors were conducted.
RESULTS: A total of 423 of 536 initially reactive donors were interviewed between 2003 and 2006: 292 confirmed-positive for WNV and 131 false-positive. Individual symptoms were not significant predictors of WNV infection, except skin rash in the week before donation (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.9) and body aches in the period after donation (OR, 2.8; 95% CI, 1.1-7.4). Specific combinations of symptoms were not good predictors of infection, but donors with three or more concurrent symptoms before donation were more likely to have WNV infection (OR, 2.5; 95% CI, 1.2-5.1). Demographic characteristics, predonation symptoms, and serology profiles in confirmed-positive donors did not predict postdonation symptom severity. Thirty-five confirmed-positive donors (12%) sought medical care for WNV infection, with two hospitalizations, but no cases of neuroinvasive disease.
CONCLUSION: The number rather than type of symptoms is associated with confirmed WNV infection, but the overall predictive value is low. Very few infected donors develop clinically significant disease.     

West Nile virus infection transmitted by blood transfusion

BACKGROUND: A patient with transfusion-transmitted West Nile virus (WNV) infection confirmed by viral culture of a blood component is described. A 24-year-old female with severe postpartum hemorrhage developed fever, chills, headache, and generalized malaise after transfusion of 18 units of blood components; a serum sample and the cerebrospinal fluid tested positive for the presence of WNV IgM antibodies. An investigation was initiated to determine a possible association between transfusion and WNV infection. STUDY DESIGN AND METHODS: Blood donors were assessed for recent infection through questionnaires and WNV testing of serum samples. Whole-blood retention segments and untransfused blood components were sent to the CDC to test for the presence of WNV through PCR (TaqMan, Applied Biosystems), IgM ELISA, plaque reduction neutralization testing, and viral culture. RESULTS: Three of 15 available donor retention segments were WNV PCR-positive. WNV was recovered from one associated blood component. The implicated donor was symptomatic near the time of donation; serology confirmed WNV IgM seroconversion. CONCLUSION: Seroconversion of a symptomatic donor, the presence of viral genetic material in an associated whole-blood retention segment, and recovery of WNV from an associated component provides compelling evidence for transfusion-acquired infection. This report has important implications for blood safety.     

West Nile virus infection in children

West Nile virus (WNV) is an emerging flavivirus responsible for an increasing number of outbreaks of neuroinvasive disease in North America, Europe, and neighboring countries. Almost all WNV infections in humans are transmitted through the bite of infected mosquitoes. Transmission during pregnancy and through breastfeeding has been reported, but the risk seems to be very low. West Nile disease in children is less common (1–5% of all WNV cases) and associated with milder symptoms and better outcome than in elderly individuals, even though severe neuroinvasive disease and death have been reported also among children. However, the incidence of WNV infection and disease in children is probably underestimated and the disease spectrum is not fully understood because of lack of reporting and underdiagnosis in children. Infection is diagnosed by detection of WNV-specific antibodies in serum and WNV RNA in plasma and urine. Since no effective WNV-specific drugs are available, therapy is mainly supportive.     

West Nile virus infection in blood donors in the New York City area during the 2010 seasonal epidemic

BACKGROUND: A uniform threshold strategy for converting from minipool (MP)‐nucleic acid testing (NAT) to individual donation (ID)‐NAT screening for acute West Nile virus (WNV) infection among blood donors is lacking. We report on WNV screening at the New York Blood Center during the 2010 seasonal WNV epidemic, the most severe epidemic in that state since the original outbreak in 1999. STUDY DESIGN AND METHODS: Between July 1 and October 31, 2010, blood donations were screened by MP‐NAT or ID‐NAT and the presence of anti‐WNV immunoglobulin (Ig)M and IgG was evaluated among NAT‐positive donations. RESULTS: Twenty presumed viremic donations were identified for a frequency of 0.0129% (1 in 7752 donations). Nine donations that could have been missed by MP‐NAT were identified. Two of these donations were both IgM and IgG negative, one of which would have been missed if more than one positive donation was required for initiating ID‐NAT. Retrospective ID‐NAT revealed two positive donations. The majority of the NAT‐positive donations in New York (16/19) were from donors who lived in counties that had the highest incidence of human WNV cases in the state. CONCLUSION: Our data details the identification of WNV NAT‐positive blood donations during a severe seasonal epidemic in the New York area. By initiating ID‐NAT after one positive donation, using retrospective testing, and triggering ID‐NAT regionally, we were able to prevent the release of presumably infectious donations. The detection of NAT‐positive donations with retrospective testing, however, may indicate the need for changes in our trigger criteria.     

Serologic diagnosis of West Nile virus infection

The epidemic of West Nile virus (WNV) in the USA in 2002 represents the largest outbreak of meningoencephalitis in the Western Hemisphere ever reported. Besides natural transmission by mosquitoes, five new modes of WNV transmission to humans have been reported: blood transfusion, organ transplantation, transplacental transmission, breastfeeding and laboratory-acquired infection. The recognition of these new transmission routes has made the development of rapid and accurate serological diagnosis of WNV infection a public health priority. In this article, the current serologic assays for WNV diagnosis are reviewed, including immunoglobulin M antibody-capture ELISA, immunoglobulin G ELISA, indirect fluorescent antibody tests, hemagglutination inhibition tests and plaque reduction neutralization tests. The recently developed immunoassays that use purified recombinant envelope and nonstructural protein 5 of WNV as antigens are also reviewed. The nonstructural protein 5 protein-based assay can reliably discriminate between WNV and dengue or St. Louis encephalitis virus, as well as between natural WNV infection and flavivirus vaccination.     

West Nile virus infection and its neurological manifestations

The West Nile virus caused an epidemic of meningoencephalitis in Midwest North America during 2002. The peak incidence coincided with the highest activity period of mosquito vectors in affected states. This epidemic followed recent established trends, not only of increased central nervous system involvement by the virus, but also increased incidence of dramatic neuromuscular impairment. Two cases are presented which illustrate the most concerning types of neuromuscular sequelae, diffuse weakness leading to respiratory insufficiency, and the development of focal weakness similar to poliomyelitis. The epidemiology and clinical characteristics of West Nile virus infection are also reviewed. Concern is expressed regarding the possibility of epidemics in other Midwestern states during future seasons of increased mosquito activity.     

West Nile virus infection in a renal transplant recipient.

This case represents the need for total teamwork in the assessment, diagnosis, and treatment of an immunosuppressed patient with a viral syndrome. One of the most striking features of this case study is the importance of a thorough history of current events and exposures in determining the list of potential diagnoses. The systematic process of laboratory evaluations to determine viral activity in an immunosuppressed patient is paramount in identifying the actual culprit responsible for the myriad of clinical symptoms at presentation. The symptomatology would guide one to the common viruses, but the travel history was the clue to testing for an uncommon etiology. The input from family members relating to the progression of mental status changes was also an important part of the current medical history. Along with supportive treatment, the patient was also given a course of interferon alpha as part of an experimental protocol. The support of the family during this decision-making process was an important function of the entire team. The patient was unable to participate in this decision and the family required a great deal of discussion regarding the pros and cons of their decision. For this patient, the outcomes were excellent. He has stable renal function, has no neurologic residual, and is back to his baseline physically and psychologically. An important recommendation based on this case is to provide educational materials to all transplant patients on viral illnesses. Topics covered should include modes of transmission, symptomatology, and the consequences of the illness. The CDC has excellent materials on West Nile Virus that can be downloaded and provided to all patients. In addition, a thorough medical history should always be obtained including possible exposures and recent travel.     

Development of effective therapies against West Nile virus infection

Since its entry into North America in 1999, West Nile virus has spread throughout the USA and Canada, and now annually causes a clinical spectrum of human disease ranging from a self-limiting acute febrile illness to potentially lethal encephalitis. Although no therapy is currently approved for use in humans, several strategies are being pursued to develop effective prophylaxis and treatments. This review describes the epidemiology, clinical presentation and pathogenesis of West Nile virus infection, and highlights recent progress towards an effective therapy.     

Development of effective therapies against West Nile virus infection

Since its entry into North America in 1999, West Nile virus has spread throughout the USA and Canada, and now annually causes a clinical spectrum of human disease ranging from a self-limiting acute febrile illness to potentially lethal encephalitis. Although no therapy is currently approved for use in humans, several strategies are being pursued to develop effective prophylaxis and treatments. This review describes the epidemiology, clinical presentation and pathogenesis of West Nile virus infection, and highlights recent progress towards an effective therapy.