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West Nile virus (WNV) is a widespread and devastating disease, especially in those who develop neuroinvasive disease. A growing body of evidence describes sequelae years after infection, including neurological complications and chronic kidney disease (CKD). Eighty-nine out of 373 WNV-positive cases were followed for approximately two years and compared to 127 WNV-negative controls with and without CKD. Adjusted risk ratios (aRRs) were calculated via a log binomial regression to determine the impact of WNV exposure and other possible confounders on the likelihood of developing CKD. Cytokine profiles of WNV patients and controls were evaluated to characterize differences and describe potential underlying pathophysiological mechanisms. The associated risk for developing CKD was significantly associated with history of WNV infection (aRR = 1.91, 95% CI 1.13-3.25). Additionally, five distinct cytokines were found to be significantly associated with WNV infection (eotaxin, IL-8, IL-12p70, IP-10, and TNFα) after the p -value was adjusted to <0.0019 due to the Bonferroni correction. These data support that WNV infection is an independent risk factor for CKD, even after accounting for confounding comorbidities. WNV participants who developed CKD had high activity of proinflammatory markers, indicating underlying inflammatory disease. This study provides new insights into CKD resultant of WNV infection.

Background: WNV causes 1.4% of all central nervous system infections and is the most common cause of epidemic neuro-invasive disease in humans., Objectives: Our main objective was to investigate retrospectively West Nile virus neuroinvasive disease (WNND) cases hospitalized during 2010-2017 and identified factors that can influence prognosis., Study Design: We documented the demographic, epidemiologic, clinical and laboratory data of WNND and identified factors that can influence prognosis. The data were recruited through Infectious Diseases International Research Initiative (ID-IRI), which serves as a network for clinical researches., Results: We investigated 165 patients with WNND in 10 countries from three continents. 27 patients died and the mortality rate was 16.4%. In an univariate analysis age, congestive heart failure, neoplasm and ischemic heart disease (p < 0.001), neuropsychiatric disorders (p = 0.011), chronic hepatitis (p = 0.024) and hypertension (p = 0.043) were risk factors for death. Fatal evolution was also correlated with ICU addmission, disorientation, speech disorders, change in consciousnes, coma, a low Glasgow coma score, obtundation, confusion (p < 0.001), history of syncope (p = 0.002) and history of unconsciousness (p = 0.037). In a binomial logistic regresssion analysis only age and coma remained independent prediction factors for death. We created an equation that was calculated according to age, co-morbidities and clinical manifestations that may be used to establish the prognosis of WNND patients., Conclusions: WNND remain an important factor for morbidity and mortality worldwide, evolution to death or survival with sequelae are not rare. Our study creates an equation that may be used in the future to establish the prognosis of WNND patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the United States, the most commonly diagnosed arboviral disease is West Nile virus (WNV) infection. Diagnosis is made by detecting WNV IgG or viral genomic sequences in serum or cerebrospinal fluid. 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. We identified 751 patients (567 adults, 184 children), among whom 390 (52%) experienced illness onset during WNV season (June-October). WNV testing was ordered for 281 (37%) of the 751; results indicated acute infection for 32 (11%). 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.

West Nile virus (WNV) has emerged as an important vector-borne pathogen in North America, with more than 3 million estimated to have been infected. Retinopathy from WNV infection has been previously reported in acute cases, though those prior reports did not evaluate the risk of retinopathy based on clinical severity of neurologic disease. The purpose of this cross-sectional study was to perform comprehensive ophthalmological and neurological examinations on 111 patients with a history of West Nile virus infection and describe the ocular manifestations. Out of 111 patients, 27 (24%) had evidence for West Nile virus associated retinopathy (WNVR); this observation was higher (49%) in those patients who initially presented with encephalitis. Individuals with WNVR had more frequent involvement of the macula and peripheral involvement compared to those patients without WNVR (p<0.05). WNVR was also associated with a greater likelihood of abnormal reflexes on neurological exam, poorer learning, greater dependence in activities of daily living, and lower quality of life (p<0.05). WNVR was seen more frequently in elderly patients (age > 60 years), and was associated with higher rates of diabetes mellitus and a history of encephalitis (p<0.05). A multivariable logistic regression revealed that only a history of encephalitis was independently associated with WNVR [Adjusted Odds Ratio = 4.9 (1.8-13.2); p = 0.001]. Our study found that WNVR occurs in one fourth of patients with a history of WNV infection and is more frequently observed in those with apparent severe neurological sequelae (e.g., encephalitis). The clinical relevance of WNVR was supported by its associations with dependence in activities of daily living and lower quality of life. This unique evaluation of WNV patients included fundoscopic examinations and their associations with neurologic impairment. Our findings can be used during ophthalmological consultation for the evaluation, treatment and rehabilitation phases of care for WNV patients.

The Houston West Nile Cohort (HWNC) was founded in 2002 when West Nile virus (WNV) reached Houston, TX. The long-term outcomes following WNV infection are still mostly unknown, though neurological abnormalities up to 1 year postinfection have been documented. We report an observational study of neurological abnormalities at 1-3 and 8-11 years following WNV infection in the HWNC. We conducted standard neurological examinations at two separate time points to assess changes in neurological status over time. The majority of patients (86%, 30/35) with encephalitis had abnormal neurological exam findings at the time of the first assessment compared with uncomplicated fever (27%, 3/11) and meningitis (36%, 5/14) cases. At the time of the second assessment, 57% (4/7) of West Nile fever (WNF), 33% (2/6) of West Nile meningitis (WNM), and 36% (5/14) of West Nile encephalitis (WNE) had developed new neurological complications. The most common abnormalities noted were tandem gait, hearing loss, abnormal reflexes, and muscle weakness. Long-term neurological abnormalities were most commonly found in patients who experienced primary WNV encephalitis. New abnormalities may develop over time regardless of initial clinical infection. Future studies should aim to differentiate neurological consequences due to WNV neuroinvasive infection versus neurological decline related to comorbid conditions., (© The American Society of Tropical Medicine and Hygiene.)

West Nile virus (WNV) is a widespread global pathogen that results in significant morbidity and mortality. Data from animal models provide evidence of persistent renal and neurological infection from WNV; however, the possibility of persistent infection in humans and long-term neurological and renal outcomes related to viral persistence remain largely unknown. In this paper, we provide a review of the literature related to persistent infection in parallel with the findings from cohorts of patients with a history of WNV infection. The next steps for enhancing our understanding of WNV as a persistent pathogen are discussed., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. Methods: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. Results: We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. Conclusions: Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit. [ABSTRACT FROM AUTHOR]

Emerging vector-borne and zoonotic pathogens can cause neuroinvasive disease in children; utilization of appropriate diagnostic testing can be low, hindering diagnosis and clinical management of these cases. We must understand factors that influence healthcare providers' decisions to order diagnostic testing. We reviewed medical charts for pediatric meningitis and encephalitis patients (90 days–18 years) between 2010 and 2017 and analyzed variables associated with testing for known neuroinvasive zoonotic pathogens in the southern United States: West Nile virus (WNV), Bartonella spp., and Rickettsia spp. Among 620 cases of meningitis and encephalitis, ~1/3 (n = 209, 34%) were tested for WNV. Fewer cases were tested for Bartonella (n = 77, 12%) and Rickettsia (n = 47, 8%). Among those tested, 14 (7%) WNV, 7 (9%) Bartonella, and 6 (13%) Rickettsia cases were identified. Factors predicting testing were similar between all agents: clinical presentation of encephalitis, focal neurologic symptoms, new onset seizure, and decreased Glasgow Coma Scale on admission. Cases with a history of arthropod contact were more likely to be tested; however, we did not see an increase in testing during the summer season, when vector exposure typically increases. While our test utilization was higher than that reported in other studies, improvement is needed to identify zoonotic causes of neuroinvasive diseases. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) infections continue to be associated with significant neurological morbidity and mortality despite various existing therapies. Adjunctive steroid therapy has been employed clinically to reduce inflammation in the treatment of CNS infections across various causative pathogens. Steroid therapy can potentially improve clinical outcomes including reducing mortality rates, provide no significant benefit, or cause worsened outcomes, based on the causative agent of infection. The data on benefits or harms of adjunctive steroid therapy is not consistent in outcome or density through CNS infections, and varies based on the disease diagnosis and pathogen. We summarize the existing literature on the effects of adjunctive steroid therapy on outcome for a number of CNS infections, including bacterial meningitis, herpes simplex virus, West Nile virus, tuberculosis meningitis, cryptococcal meningitis, Angiostrongylus cantonensis , neurocysticercosis, autoimmune encephalitis, toxoplasmosis, and bacterial brain abscess. We describe that while steroid therapy is beneficial and supported in pathogens such as pneumococcal meningitis and tuberculosis, for other diseases, like Listeria monocytogenes and Cryptococcus neoformans they are associated with worse outcomes. We highlight areas of consistent and proven findings and those which need more evidence for supported beneficial clinical use of adjunctive steroid therapy. [ABSTRACT FROM AUTHOR]

To understand the long-term neurological outcomes resultant of West Nile virus (WNV) infection, participants from a previously established, prospective WNV cohort were invited to take part in a comprehensive neurologic and neurocognitive examination. Those with an abnormal exam finding were invited for MRI to evaluate cortical thinning and regional brain atrophy following infection. Correlations of presenting clinical syndrome with neurologic and neurocognitive dysfunctions were evaluated, as well as correlations of neurocognitive outcomes with MRI results. From 2002 to 2012, a total of 262 participants with a history of WNV infection were enrolled as research participants in a longitudinal cohort study, and 117 completed comprehensive neurologic and neurocognitive evaluations. Abnormal neurological exam findings were identified in 49% (57/117) of participants, with most abnormalities being unilateral. The most common abnormalities included decreased strength (26%; 30/117), abnormal reflexes (14%; 16/117), and tremors (10%; 12/117). Weakness and decreased reflexes were consistent with lower motor neuron damage in a significant proportion of patients. We observed a 22% overall rate of impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), with impairments observed in immediate (31%) and delayed memory (25%). On MRI, participants showed significant cortical thinning as compared to age- and gender-matched controls in both hemispheres, with affected regions primarily occurring in the frontal and limbic cortices. Regional atrophy occurred in the cerebellum, brain stem, thalamus, putamen, and globus pallidus. This study provides valuable new information regarding the neurological outcomes following WNV infection, with MRI evidence of significant cortical thinning and regional atrophy; however, it is important to note that the results may include systemic bias due to the external control group. Considering no effective treatment measures are available, strategies to prevent infection are key. [ABSTRACT FROM AUTHOR]

Introduction: Neuromuscular clinical manifestations during acute West Nile virus (WNV) infection are well documented; however, long-term neurologic outcomes still require investigation.Methods: We conducted a long-term follow-up study in patients with history of WNV infection. Of the 117 patients who participated in neurologic and neurocognitive evaluations, 30 were referred for neuromuscular and electrodiagnostic evaluation based on abnormal findings.Results: We found that 33% of these patients (10 of 30) showed abnormalities on nerve conduction and/or needle electromyography due to primary or secondary outcomes of WNV infection. Most common electrodiagnostic findings and causes of long-term disability were related to anterior horn cell poliomyelitis (WNV poliomyelitis). Electrical data on these patient populations were similar to those observed in chronic poliomyelitis.Discussion: With more than 16,000 cases of WNV neuroinvasive disease reported across the USA since 1999, understanding clinical outcomes from infection will provide a resource for physicians managing long-term care of these patients. Muscle Nerve 57: 77-82, 2018. [ABSTRACT FROM AUTHOR]

Abstract: Background: Toscana virus (TOSV) is an emerging pathogen causing central nervous system (CNS) infection in Mediterranean countries, mostly during summer season. Objectives: To compare the clinical and laboratory characteristics of Toscana CNS infections to the most common viral pathogens seen in the United States. Study design: We performed a case series of patients with 41 TOSV infection and compared the clinical characteristics, laboratory findings, imaging results and clinical outcomes to the most commonly recognized viral causes of meningoencephalitis in the US [enterovirus (n =60), herpes simplex virus (n =48), and West Nile virus (n =30)] from our multi-center study of patients with aseptic meningoencephalitis syndromes in the Greater Houston area. Results: TOSV infection occurs in different age groups compared to enterovirus, HSV, and WNV. All infections most frequently occur during summer–fall except HSV which distributes throughout the year. All patients with TOSV had history of travel to endemic areas. There are differences in clinical presentation and CSF findings comparing TOSV and enterovirus, HSV, and WNV infection. There are no significant differences in outcomes of each infection except WNV meningoencephalitis which had a poorer outcome compared to TOSV infection. Conclusions: TOSV is an emerging pathogen that should be considered in the differential diagnosis of patients with CNS infections and a recent travel history to endemic areas. [Copyright &y& Elsevier]

• Cytomegalovirus meningoencephalitis occurs primarily in immunocompromised patients. • Encephalitis is the dominant presentation. • Clinical and laboratory findings differ from other viral etiologies. • Outcomes are significantly worse compared to enterovirus, HSV and VZV. Hallmarks of cytomegalovirus (CMV) meningoencephalitis include fever, altered mental status, or meningismus with pleocytosis, elevated protein and hypoglycorrhachia on cerebrospinal fluid (CSF) analysis. Magnetic resonance imaging may show ventriculitis, ependymitis or periventricular enhancement. Studies are limited comparing clinical and laboratory characteristics to other viral etiologies. This multi-center, retrospective cohort analysis reviewed patients with CMV meningitis or encephalitis and compared clinical features, laboratory findings and outcomes to the most common viral causes of meningoencephalitis. Patients with encephalitis or aseptic meningitis and detectable genetic material by polymerase chain reaction were identified. Clinical characteristics, laboratory findings and neuroimaging were collected from the electronic medical record. Data analysis was performed comparing CMV to other viral etiologies. 485 patients were evaluated and included cases of CMV (n = 36) which were compared with herpes simplex virus (n = 114), enterovirus (n = 207), varicella zoster virus (n = 41) and West Nile virus (n = 81). Human immunodeficiency virus (HIV) infection was seen more frequently in CMV infection compared with all other viral etiologies. Clinical presentations and CSF findings of other viral etiologies differ compared with CMV. Hypoglycorrhacia occurred more often with CMV compared with other viral pathogens. Outcomes were significantly worse compared with enterovirus, herpes simplex virus and varicella zoster virus but not West Nile virus. CMV meningoencephalitis occurs most often in patients with HIV and encephalitis occurs more frequently than meningitis. Clinical and laboratory findings differ compared with other viral etiologies and can support consideration of CMV in the differential diagnosis of patients with meningoencephalitis [ABSTRACT FROM AUTHOR]