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Immunoassays for WNV-specific IgM are available commercially and through state public health laboratories.
WNV-specific IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented.
Therefore, positive IgM antibodies occasionally may reflect a past infection. If serum is collected within 8 days of illness onset, the absence of detectable virus-specific IgM does not rule out the diagnosis of WNV infection, and the test may need to be repeated on a later sample.
The presence of WNV-specific IgM in blood or CSF provides good evidence of recent infection but may also result from cross-reactive antibodies after infection with other flaviviruses or from non-specific reactivity.
According to product inserts for commercially available WNV IgM assays, all positive results obtained with these assays should be confirmed by neutralizing antibody testing of acute- and convalescent-phase serum specimens at a state public health laboratory or CDC. WNV IgG antibodies generally are detected shortly after IgM antibodies and persist for many years following a symptomatic or asymptomatic infection.
Therefore, the presence of IgG antibodies alone is only evidence of previous infection and clinically compatible cases with the presence of IgG, but not IgM, should be evaluated for other etiologic agents. Plaque-reduction neutralization tests PRNTs performed in reference laboratories, including some state public health laboratories and CDC, can help determine the specific infecting flavivirus.
Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. For CME questions, see this page. Release date: August 10, ; Expiration date: August 10, Disclosure: P. Charles P. Disclosure: Charles P.
Vega, MD, has disclosed the following financial relationships: served as an advisor or consultant for Allergan, Inc.
To determine frequency of this testing in WNV-endemic areas, we examined the proportion of tests ordered for patients with meningitis and encephalitis at 9 hospitals in Houston, Texas, USA. Characteristics associated with WNV testing were acute focal neurologic deficits; older age; magnetic resonance imaging; empirically prescribed antiviral therapy; worse clinical outcomes: and concomitant testing for mycobacterial, fungal, or other viral infections.
Testing for WNV is underutilized, and testing of patients with more severe disease raises the possibility of diagnostic bias in epidemiologic studies. Arboviruses arthropodborne viruses are viruses that can infect humans via arthropod vectors, including mosquitoes, ticks, and sand flies.
In the United States, the most common arboviral disease is infection with West Nile virus WNV , which is transmitted largely by mosquitoes of the genus Culex. WNND is characterized by encephalitis and meningitis and sometimes rarely acute flaccid paralysis 7 , 8. Despite the availability of sensitive testing for WNV, serologic testing is often underutilized, probably because of lack of physician awareness.
Underutilization of testing contributes to multiple biases e. Accurate data about patterns of WNV utilization in routine clinical practice is needed for enhancement and tailoring of future public health interventions. Patients with acute flaccid paralysis were included only if they had concomitant meningitis or encephalitis. Exclusion criteria were CSF positivity by Gram stain for bacteria or yeast from cytospin samples, past craniotomy, or current ventriculoperitoneal shunt.
Baseline clinical characteristics were recorded at the time the patient was seen in the emergency department and included demographic data, concurrent conditions determined by Charlson Comorbidity Index , immunologic status, clinical features including neurologic examination findings and Glasgow Coma Scale scores , laboratory test results, and case management.
Empirical treatment was defined as initiation of antibacterial or antiviral agents before the results of the CSF cultures or molecular diagnostic methods were available.
Participant outcomes were assessed at the time of discharge from the hospital by using Glasgow Outcome Scale scores 17 : a score of 1 indicates death; 2, a vegetative state inability to interact with the environment ; 3, severe disability unable to live independently but follows commands ; 4, moderate disability able to live independently but unable to resume some previous activities, at work or in social life ; and 5, mild or no disability able to resume normal activities with minimal to no physical or mental deficits.
An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 1—4. Etiologies of meningitis and encephalitis were divided into 6 categories bacterial, viral, fungal, mycobacterial, noninfectious, and unknown , according to the final diagnosis when participants were discharged from the hospital.
General arbovirus serology panels for St. Louis encephalitis, Eastern equine encephalitis, and Western equine encephalitis viruses were performed by indirect fluorescence antibody assay at the Associated Regional and University Pathologists laboratory Houston, TX, USA.
The diagnosis was acute infection from other arboviruses when samples were positive for specific arboviral IgM in the absence of evidence of WNV infection. Baseline and clinical characteristics having a clinically plausible association with suspicion of WNV and other arboviral infections were examined by bivariate analysis.
We examined continuous data by using analysis of variance. During the study period, patients with a diagnosis of meningitis or encephalitis were screened for eligibility. We excluded patients for the following reasons: positive Gram stain patients , presence of shunt 84 patients , and postcraniotomy meningitis 17 patients. No difference between testing status tested or not tested groups was found in terms of Charlson Comorbidity Index scores or HIV status.
Per inclusion criteria, all participants had undergone lumbar puncture and had evidence of CSF pleocytosis Table 3. Numbers of patients for whom West Nile virus serologic testing was performed, by month, combined over 5 years January 1, , through December 31, A total of patients were All positive results for these 32 patients were obtained during June—October, as demonstrated in the epidemiologic curve Figure. Louis encephalitis virus were positive. Among these 11 patients, positive WNV serologic results were compatible with acute WNV infection for 7, indicating the possibility of cross-reaction.
However, for 4 patients, WNV serologic results were negative, compatible with their having true acute infection with St. Louis encephalitis virus. Our evaluation of the use of WNV diagnostics for patients with meningitis and encephalitis in routine clinical practice in a WNV-endemic area indicates that most cases were of unknown etiology.
This finding is similar to that of the California Encephalitis Project In our study, this finding can be explained by underutilization of testing in this patient population. This difference could be explained by an epidemiologic difference in the circulation of WNV because more cases were reported from Texas than from California during the study periods 1.
As previously reported, we found that arboviral infections were more commonly diagnosed for adults Furthermore, no patients in our study were tested for La Crosse encephalitis; such testing would have enabled a more specific comparison of accuracy. Patients with clinical features of encephalitis altered mental status, abnormal Glasgow Coma Scale score, or focal neurologic abnormalities were tested for WNV more frequently. Therefore, meningitis should be recognized as a common manifestation of WNND, and appropriate testing should be conducted.
This information supports a decision to routinely send specimens collected during June—October for WNV testing. Patients tested for WNV infection were more likely to empirically be given antiviral therapy and to undergo evaluations for mycobacterial, fungal, and other viral infections Moreover, patients for whom WNV serum testing was ordered were more likely to undergo brain magnetic resonance imaging and to experience adverse clinical outcomes; these factors are probably driven by a more severe clinical presentation because most patients had encephalitis.
Of note, patients with a diagnosis of viral meningitis or encephalitis were less likely to be tested for WNV. This finding probably resulted from testing for WNV after receiving negative results for routine viral testing including PCR for herpes simplex virus and enterovirus. Unfortunately, because of the design of this study, we are unable to go back and test those for whom samples were not submitted for WNV testing at the time of their illness to determine the number of cases missed because testing was not performed.
According to the Centers for Disease Control and Prevention, laboratory-confirmed acute WNV cases must meet specific diagnostic criteria; however, recent evidence of IgM persistence in WNV-positive patients has affected our ability to diagnosis true acute cases 1. As a result, patients with an isolated positive WNV IgM result in serum are considered to have a probable case. RT-PCR for WNV is an alternative diagnostic tool for acute infection, but its application is limited because viremia is typically undetectable by the time symptoms appear.
The usefulness of RT-PCR is further complicated by the fact that median time of symptom onset to actual testing is 13 days
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