|
1
|
Roberts JA, Kim CY, Hwang SA, Hassan A, Covington E, Heydari K, Lyerly M, Sejvar JJ, Hasbun R, Prasad M, Thakur KT. Clinical, Prognostic, and Longitudinal Functional and Neuropsychological Features of West Nile Virus Neuroinvasive Disease in the United States: A Systematic Review and Meta-Analysis. Ann Neurol 2025. [PMID: 40008684 DOI: 10.1002/ana.27220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 01/26/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025]
Abstract
OBJECTIVE West Nile virus (WNV) is the most common cause of arboviral disease in the United States. Approximately 1% of infections involve the nervous system, most commonly resulting in West Nile encephalitis (WNE), West Nile meningitis (WNM), or acute flaccid paralysis (AFP). METHODS In this systematic review, we characterized comprehensively the diagnostic and clinical features of WNV neuroinvasive disease (WNND) in the United States, as well as the evidence regarding prognostic factors and long-term outcomes of WNND. RESULTS We identified 47 relevant studies reporting data on acute or longitudinal features of WNND. Across studies, the most common presenting symptoms were fever (88%), nausea/vomiting (58%), and fatigue (50%) coupled neurologically with headache (50%), altered mental status (39%), and focal weakness (32%). Pooled mortality was 9.2%, and 42.1% of reported cases required intensive care unit (ICU) admission. In meta-analyses, chronic kidney disease (odds ratio [OR] = 5.99, 95% confidence interval [CI] = 2.71-13.23), diabetes mellitus (OR = 2.43, 95% CI = 1.54-3.84), and hypertension (OR = 4.01, 95% CI = 2.39-6.72) were associated with an increased risk of mortality. Multidomain neurocognitive impairment was reported in several studies at post-hospitalization follow-up, although with marked heterogeneity between study methodology. Subjective neurocognitive impairment, most notably fatigue (37-75%), memory concerns (11-57%), concentration deficits (17-48%), and depression (17-38%), were also common at post-hospitalization follow-up. INTERPRETATION These findings underscore the significant mortality and morbidity of WNND in the acute and long-term setting. Our findings may additionally provide utility for risk stratification of hospitalized patients with WNND and suggest the need for further evaluation of novel therapeutics to prevent substantial disease-associated acute and long-term disability. ANN NEUROL 2025.
Collapse
Affiliation(s)
- Jackson A Roberts
- Program in Neuroinfectious Diseases, Department of Neurology, Columbia University Irving Medical Center, New York, NY
- Department of Neurology, Massachusetts General Brigham, Boston, MA
| | - Carla Y Kim
- Program in Neuroinfectious Diseases, Department of Neurology, Columbia University Irving Medical Center, New York, NY
| | | | - Amir Hassan
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA
| | - Ethan Covington
- Xavier University of Louisiana, New Orleans, LA
- STAR U Program, Department of Neurology, Columbia University Irving Medical Center, New York, NY
| | | | - Mac Lyerly
- Wake Forest University School of Medicine, Winston-Salem, NC
| | - James J Sejvar
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Rodrigo Hasbun
- Division of Infectious Diseases, Department of Internal Medicine, University of Texas-Houston, Houston, TX
| | - Manya Prasad
- Clinical Research and Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kiran T Thakur
- Program in Neuroinfectious Diseases, Department of Neurology, Columbia University Irving Medical Center, New York, NY
| |
Collapse
|
|
2
|
Mielcarska MB, Rouse BT. Viruses and the Brain-A Relationship Prone to Trouble. Viruses 2025; 17:203. [PMID: 40006958 PMCID: PMC11860391 DOI: 10.3390/v17020203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/23/2025] [Accepted: 01/28/2025] [Indexed: 02/27/2025] Open
Abstract
Neurological disorders, some of which are associated with viral infections, are growing due to the aging and expanding population. Despite strong defenses of the central nervous system, some viruses have evolved ways to breach them, which often result in dire consequences. In this review, we recount the various ways by which different viruses can enter the CNS, and we describe the consequences of such invasions. Consequences may manifest as acute disease, such as encephalitis, meningitis, or result in long-term effects, such as neuromuscular dysfunction, as occurs in poliomyelitis. We discuss evidence for viral involvement in the causation of well-known chronic neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as vascular dementia in the elderly. We also describe the approaches currently available to control a few of the neural viral infections. These include antivirals that are effective against human immunodeficiency virus and herpes simplex virus, as well as vaccines valuable for controlling rabies virus, poliomyelitis virus, and some flavivirus infections. There is an urgent need to better understand, at a molecular level, how viruses contribute to acute and, especially, chronic neurological diseases and to develop more precise and effective vaccines and therapies.
Collapse
Affiliation(s)
- Matylda Barbara Mielcarska
- Department of Preclinical Sciences, Institute of Veterinary Sciences, Warsaw University of Life Sciences–SGGW, Jana Ciszewskiego 8, 02-786 Warsaw, Poland
| | - Barry T. Rouse
- College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA
| |
Collapse
|
|
3
|
Cody SG, Adam A, Siniavin A, Kang SS, Wang T. Flaviviruses-Induced Neurological Sequelae. Pathogens 2024; 14:22. [PMID: 39860983 PMCID: PMC11768111 DOI: 10.3390/pathogens14010022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/24/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
Flaviviruses, a group of single-stranded RNA viruses spread by mosquitoes or ticks, include several significant neurotropic viruses, such as West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Zika virus (ZIKV). These viruses can cause a range of neurological diseases during acute infection, from mild, flu-like symptoms to severe and fatal encephalitis. A total of 20-50% of patients who recovered from acute flavivirus infections experienced long-term cognitive issues. Here, we discuss these major neurotropic flaviviruses-induced clinical diseases in humans and the recent findings in animal models and provide insights into the underlying disease mechanisms.
Collapse
Affiliation(s)
- Samantha Gabrielle Cody
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (S.G.C.); (A.A.); (A.S.); (S.S.K.)
- Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Awadalkareem Adam
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (S.G.C.); (A.A.); (A.S.); (S.S.K.)
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Andrei Siniavin
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (S.G.C.); (A.A.); (A.S.); (S.S.K.)
| | - Sam S. Kang
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (S.G.C.); (A.A.); (A.S.); (S.S.K.)
| | - Tian Wang
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (S.G.C.); (A.A.); (A.S.); (S.S.K.)
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
- Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
- Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
| |
Collapse
|
|
4
|
Ai S, Arutyunov A, Liu J, Hill JD, Jiang X, Klein RS. CCR2 restricts IFN-γ production by hippocampal CD8 TRM cells that impair learning and memory during recovery from WNV encephalitis. J Neuroinflammation 2024; 21:330. [PMID: 39725999 DOI: 10.1186/s12974-024-03309-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/21/2024] [Indexed: 12/28/2024] Open
Abstract
Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-γ contribute to neurodegenerative processes, including synapse loss, leading to memory impairment. Here, we show that CCR2 signaling in CD8 TRM that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 TRM during WNV recovery reveal that CCR2 signaling significantly regulates hippocampal CD8 TRM phenotype and function via extrinsic and intrinsic effects, limiting expression of CD103, granzyme A and IFN-γ, respectively, and increasing the percentages of virus-specific CD8 T cells. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Overall, these data implicate CCR2 signaling in the regulation of CD8 TRM phenotype, including antiviral specificity and IFN-γ expression, highlighing a neuroprotective role for CCR2 in limiting CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.
Collapse
Affiliation(s)
- Shenjian Ai
- Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Artem Arutyunov
- Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Joshua Liu
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Jeremy D Hill
- Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Canada
| | - Xiaoping Jiang
- Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Robyn S Klein
- Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
| |
Collapse
|
|
5
|
Ai S, Arutyunov A, Liu J, Hill JD, Jiang X, Klein RS. CCR2 limits inflammatory functions of CD8 TRM cells that impair recognition memory during recovery from WNV encephalitis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.09.17.613307. [PMID: 39345540 PMCID: PMC11429802 DOI: 10.1101/2024.09.17.613307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Central nervous system (CNS) resident memory CD8 T cells (T RM ) that express IFN-γ contribute to neurodegenerative processes, including synapse loss, leading to memory impairments. Here, we show that CCR2 signalling in CD8 T RM that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2 + versus CCR2 - CD8 T RM during WNV recovery reveal that CCR2 signalling significantly regulates hippocampal CD8 T RM phenotype and function via extrinsic and intrinsic effects, decreasing the expression of CD103 and granzyme A and IFN-γ, respectively. Consistent with this, WNV-recovered Cd8a cre Ccr2 fl/fl mice exhibit decreased recognition memory. Our findings highlight a neuroprotective role for CCR2 in limiting CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.
Collapse
|
|
6
|
Olsen EA, Quinones AK, Vo TL. A Case of West Nile Virus Neuroinvasive Disease Presenting With Isolated Diplopia. Cureus 2024; 16:e65777. [PMID: 39211671 PMCID: PMC11361735 DOI: 10.7759/cureus.65777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2024] [Indexed: 09/04/2024] Open
Abstract
West Nile virus (WNV) is a single-stranded RNA virus causing a wide spectrum of diseases. Neuroinvasive conditions such as meningitis and encephalitis are feared complications of WNV infection. Here, we describe the case of a 78-year-old male whose only initial presenting symptoms were fever and transient diplopia, whose initial MRI imaging with and without contrast did not reveal any abnormalities. He was discharged, only to return to care the next day; lumbar puncture was performed suggesting bacterial meningitis, and he was admitted and given antibiotics. Repeat MRI was negative, and he developed an altered mental status requiring intubation. WNV neuroinvasive disease was subsequently found after serology was performed. Supportive care was given, and he made a full recovery with no residual deficits. This case highlights an unusual presentation of WNV encephalitis and highlights the difficulty that can be present in diagnosing this disease.
Collapse
Affiliation(s)
- Elizabeth A Olsen
- Emergency Medicine, Rocky Vista University College of Osteopathic Medicine, Parker, USA
| | | | - Timothy L Vo
- Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, USA
| |
Collapse
|
|
7
|
Shih HI, Wang YP, Chi CY, Chien YW. Risks of anxiety disorders, depressive disorders, and sleep disorders in patients with dengue fever: A nationwide, population-based cohort study. PLoS Negl Trop Dis 2024; 18:e0012239. [PMID: 38959212 PMCID: PMC11221675 DOI: 10.1371/journal.pntd.0012239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 05/22/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.
Collapse
Affiliation(s)
- Hsin-I Shih
- Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Ping Wang
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli County, Taiwan
| | - Chia-Yu Chi
- National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli County, Taiwan
- Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Wen Chien
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| |
Collapse
|
|
8
|
Underwood EC, Vera IM, Allen D, Alvior J, O’Driscoll M, Silbert S, Kim K, Barr KL. Seroprevalence of West Nile Virus in Tampa Bay Florida Patients Admitted to Hospital during 2020-2021 for Respiratory Symptoms. Viruses 2024; 16:719. [PMID: 38793601 PMCID: PMC11125834 DOI: 10.3390/v16050719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 04/27/2024] [Accepted: 04/28/2024] [Indexed: 05/26/2024] Open
Abstract
West Nile virus (WNV) is an arbovirus spread primarily by Culex mosquitoes, with humans being a dead-end host. WNV was introduced to Florida in 2001, with 467 confirmed cases since. It is estimated that 80 percent of cases are asymptomatic, with mild cases presenting as a non-specific flu-like illness. Currently, detection of WNV in humans occurs primarily in healthcare settings via RT-PCR or CSF IgM when patients present with severe manifestations of disease including fever, meningitis, encephalitis, or acute flaccid paralysis. Given the short window of detectable viremia and requirement for CSF sampling, most WNV infections never receive an official diagnosis. This study utilized enzyme-linked immunosorbent assay (ELISA) to detect WNV IgG antibodies in 250 patient serum and plasma samples collected at Tampa General Hospital during 2020 and 2021. Plaque reduction neutralization tests were used to confirm ELISA results. Out of the 250 patients included in this study, 18.8% of them were IgG positive, consistent with previous WNV exposure. There was no relationship between WNV exposure and age or sex.
Collapse
Affiliation(s)
- Emma C. Underwood
- Center for Global Health and Infectious Disease Research, University of South Florida, Tampa, FL 33612, USA; (E.C.U.)
| | - Iset M. Vera
- Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Dylan Allen
- Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Joshua Alvior
- Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | | | | | - Kami Kim
- Center for Global Health and Infectious Disease Research, University of South Florida, Tampa, FL 33612, USA; (E.C.U.)
- Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
- Tampa General Hospital, Tampa, FL 33606, USA
| | - Kelli L. Barr
- Center for Global Health and Infectious Disease Research, University of South Florida, Tampa, FL 33612, USA; (E.C.U.)
| |
Collapse
|
|
9
|
Maccarone MC, Coraci D, Ragazzo L, Munari M, Piccione F, Masiero S. Rehabilitation approaches in West Nile Virus survivors: a systematic review. Eur J Phys Rehabil Med 2024; 60:113-121. [PMID: 38059575 PMCID: PMC10938036 DOI: 10.23736/s1973-9087.23.07880-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 09/05/2023] [Accepted: 11/21/2023] [Indexed: 12/08/2023]
Abstract
INTRODUCTION Periodic increases in West Nile virus (WNV) infections have been documented. Proper rehabilitative management is essential for these patients, who may experience limitations in daily activities even after the resolution of the acute infection. Since there are currently no globally accepted guidelines, our aim is to conduct a best-evidence synthesis on rehabilitative management for patients with neuroinvasive WNV. EVIDENCE ACQUISITION We screened the literature with two independent researchers conducting searches on PubMed, Embase, SCOPUS, and Google Scholar databases for WNV-related studies in the field of rehabilitation. Suitable studies were identified and selected through a rigorous process. The review includes original research articles published up to August 15, 2023. EVIDENCE SYNTHESIS Despite the potential for bias in the studies, the literature suggests that a comprehensive and interdisciplinary rehabilitation program, which includes physical therapy with neuromotor and respiratory interventions, occupational therapy, neurocognitive interventions, and speech therapy for dysphagia and communication issues, can lead to functional improvement in WNV patients. This program should be tailored to address each patient's specific challenges, and the duration of the rehabilitation program may vary depending on the individual patient's needs. CONCLUSIONS Even if additional research with larger cohorts and higher evidence levels is needed for a comprehensive understanding of WNV patient rehabilitation, an early and comprehensive rehabilitation approach addressing respiratory, neuromuscular, and cognitive aspects appears effective for WNV patient recovery.
Collapse
Affiliation(s)
- Maria C Maccarone
- Department of Neuroscience, Physical Medicine and Rehabilitation School, University of Padua, Padua, Italy -
| | - Daniele Coraci
- Unit of Neurorehabilitation, Department of Neuroscience, University of Padua, Padua, Italy
| | - Lisa Ragazzo
- Unit of Neurorehabilitation, Department of Neuroscience, University of Padua, Padua, Italy
| | - Marina Munari
- Institute of Anesthesia and Intensive Care, University Hospital of Padua, Padua, Italy
| | - Francesco Piccione
- Unit of Neurorehabilitation, Department of Neuroscience, University of Padua, Padua, Italy
| | - Stefano Masiero
- Unit of Neurorehabilitation, Department of Neuroscience, University of Padua, Padua, Italy
- Institute of Anesthesia and Intensive Care, University Hospital of Padua, Padua, Italy
| |
Collapse
|
|
10
|
Kvam KA, Stahl JP, Chow FC, Soldatos A, Tattevin P, Sejvar J, Mailles A. Outcome and Sequelae of Infectious Encephalitis. J Clin Neurol 2024; 20:23-36. [PMID: 38179629 PMCID: PMC10782093 DOI: 10.3988/jcn.2023.0240] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 10/04/2023] [Accepted: 10/23/2023] [Indexed: 01/06/2024] Open
Abstract
Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected despite their high frequency and possible severity. We reviewed the available data on sequelae and persisting symptoms following infectious encephalitis with the aim of characterizing the clinical picture of these patients at months to years after hospitalization. We searched PubMed for case series involving sequelae after infectious encephalitis. We carried out a narrative review of the literature on encephalitis caused by members of the Herpesviridae family (herpes simplex virus, varicella zoster virus, and human herpesvirus-6), members of the Flaviviridae family (West Nile virus, tick-borne encephalitis virus, and Japanese encephalitis virus), alphaviruses, and Nipah virus. We retrieved 41 studies that yielded original data involving 3,072 adult patients evaluated after infectious encephalitis. At least one of the five domains of cognitive outcome, psychiatric disorders, neurological deficits, global functioning, and quality of life was investigated in the reviewed studies. Various tests were used in the 41 studies and the investigation took place at different times after hospital discharge. The results showed that most patients are discharged with impairments, with frequent deficits in cognitive function such as memory loss or attention disorders. Sequelae tend to improve within several years following flavivirus or Nipah virus infection, but long-term data are scarce for other pathogens. Further research is needed to better understand the extent of sequelae after infectious encephalitis, and to propose a standardized assessment method and assess the rehabilitation efficacy in these patients.
Collapse
Affiliation(s)
- Kathryn A Kvam
- Department of Neurology & Neurological Sciences, Center for Academic Medicine, Stanford University, Stanford, CA, USA
| | | | - Felicia C Chow
- Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
- Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, CA, USA
| | - Ariane Soldatos
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Pierre Tattevin
- Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France
| | - James Sejvar
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Alexandra Mailles
- Department of Infectious Diseases, Santé publique France, Saint-Maurice, France.
| |
Collapse
|
|
11
|
Fu XL, Ma Y, Li Z, Qi YY, Wang SJ, Fu LJ, Wang SM, von Seidlein L, Wang XY. Cost-of-illness of gastroenteritis caused by rotavirus in Chinese children less than 5 years. Hum Vaccin Immunother 2023; 19:2276619. [PMID: 38013426 PMCID: PMC10760361 DOI: 10.1080/21645515.2023.2276619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 10/24/2023] [Indexed: 11/29/2023] Open
Abstract
Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.
Collapse
Affiliation(s)
- Xiao-Li Fu
- Key Laboratory of Medical Molecular Virology of MoE & MoH,Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Yan Ma
- Department of Infectious Disease Prevention and Control, Shaoxing Center for Disease Control and Prevention, Shaoxing, China
| | - Zheng Li
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Yang-Yang Qi
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Si-Jie Wang
- Key Laboratory of Medical Molecular Virology of MoE & MoH,Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Li-Jun Fu
- Department of Infectious Disease Prevention and Control, Shaoxing Center for Disease Control and Prevention, Shaoxing, China
| | - Song-Mei Wang
- Laboratory of Molecular Biology, Training Center of Medical Experiments, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Lorenz von Seidlein
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Xuan-Yi Wang
- Key Laboratory of Medical Molecular Virology of MoE & MoH,Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
- Children’s Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
12
|
Park H, Kwon N, Park G, Jang M, Kwon Y, Yoon Y, An J, Min J, Lee T. Fast-response electrochemical biosensor based on a truncated aptamer and MXene heterolayer for West Nile virus detection in human serum. Bioelectrochemistry 2023; 154:108540. [PMID: 37556929 DOI: 10.1016/j.bioelechem.2023.108540] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/11/2023]
Abstract
West Nile virus (WNV) is a mosquito-borne flavivirus that can cause West Nile fever, meningitis, encephalitis, and polio. Early detection of WNV is important to prevent infection spread on the field. To commercialize the electrochemical biosensor for WNV, rapid target detection with the cheap manufacture cost is essential. Here, we developed a fast-response electrochemical biosensor consisting of a truncated WNV aptamer/MXene (Ti3C2Tx) bilayer on round-type micro gap. To reduce the target binding time, the application of the alternating current electrothermal flow (ACEF) technology reduced the target detection time to within 10 min, providing a rapid biosensor platform. The MXene nanosheet improved electrochemical signal amplification, and the aptamer produced through systematic evolution of ligands by exponential enrichment process eliminated unnecessary base sequences via truncation and lowered the manufacturing cost. Under optimized conditions, the WNV limit of detection (LOD) and selectivity were measured using electrochemical measurement methods, including cyclic voltammetry and square wave voltammetry. The LOD was 2.57 pM for WNV diluted in deionized water and 1.06 pM for WNV diluted in 10% human serum. The fabricated electrochemical biosensor has high selectivity and allows rapid detection, suggesting the possibility of future application in the diagnosis of flaviviridae virus.
Collapse
Affiliation(s)
- Hanbin Park
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Nayeon Kwon
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Goeun Park
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Moonbong Jang
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Yein Kwon
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Yejin Yoon
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Jeongyun An
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea
| | - Junhong Min
- School of Integrative Engineering Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea.
| | - Taek Lee
- Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea.
| |
Collapse
|
|
13
|
Blackhurst BM, Funk KE. Molecular and Cellular Mechanisms Underlying Neurologic Manifestations of Mosquito-Borne Flavivirus Infections. Viruses 2023; 15:2200. [PMID: 38005878 PMCID: PMC10674799 DOI: 10.3390/v15112200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 10/21/2023] [Accepted: 10/25/2023] [Indexed: 11/26/2023] Open
Abstract
Flaviviruses are a family of enveloped viruses with a positive-sense RNA genome, transmitted by arthropod vectors. These viruses are known for their broad cellular tropism leading to infection of multiple body systems, which can include the central nervous system. Neurologic effects of flavivirus infection can arise during both acute and post-acute infectious periods; however, the molecular and cellular mechanisms underlying post-acute sequelae are not fully understood. Here, we review recent studies that have examined molecular and cellular mechanisms that may contribute to neurologic sequelae following infection with the West Nile virus, Japanese encephalitis virus, Zika virus, dengue virus, and St. Louis encephalitis virus. Neuronal death, either from direct infection or due to the resultant inflammatory response, is a common mechanism by which flavivirus infection can lead to neurologic impairment. Other types of cellular damage, such as oxidative stress and DNA damage, appear to be more specific to certain viruses. This article aims to highlight mechanisms of cellular damage that are common across several flavivirus members and mechanisms that are more unique to specific members. Our goal is to inspire further research to improve understanding of this area in the hope of identifying treatment options for flavivirus-associated neurologic changes.
Collapse
Affiliation(s)
| | - Kristen E. Funk
- Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
| |
Collapse
|
|
14
|
Du C, Li G, Han G. Biosafety and mental health: Virus induced cognitive decline. BIOSAFETY AND HEALTH 2023; 5:159-167. [PMID: 40078510 PMCID: PMC11895046 DOI: 10.1016/j.bsheal.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/27/2023] [Accepted: 04/10/2023] [Indexed: 03/14/2025] Open
Abstract
Biological agents threats people's life through different ways, one of which lies in the impairment of cognition. It is believed cognitive decline may result from biological agents mediated neuron damage directly, or from the activation of the host immune response to eradicate the pathogen. However, direct linkage between infections and cognitive decline is very limited. Here we focus on the mechanisms of how different biological virus or they induced systemic and local inflammation link to the cognitive impairment, focusing on the roles of activated microglia and several molecular pathways mediated neurotoxicity.
Collapse
Affiliation(s)
- Chunxiao Du
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| | - Ge Li
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| | - Gencheng Han
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| |
Collapse
|
|
15
|
McMillan RE, Wang E, Carlin AF, Coufal NG. Human microglial models to study host-virus interactions. Exp Neurol 2023; 363:114375. [PMID: 36907350 PMCID: PMC10521930 DOI: 10.1016/j.expneurol.2023.114375] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 02/13/2023] [Accepted: 03/02/2023] [Indexed: 03/14/2023]
Abstract
Microglia, the resident macrophage of the central nervous system, are increasingly recognized as contributing to diverse aspects of human development, health, and disease. In recent years, numerous studies in both mouse and human models have identified microglia as a "double edged sword" in the progression of neurotropic viral infections: protecting against viral replication and cell death in some contexts, while acting as viral reservoirs and promoting excess cellular stress and cytotoxicity in others. It is imperative to understand the diversity of human microglial responses in order to therapeutically modulate them; however, modeling human microglia has been historically challenging due to significant interspecies differences in innate immunity and rapid transformation upon in vitro culture. In this review, we discuss the contribution of microglia to the neuropathogenesis of key neurotropic viral infections: human immunodeficiency virus 1 (HIV-1), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We pay special attention to recent work with human stem cell-derived microglia and propose strategies to leverage these powerful models to further uncover species- and disease-specific microglial responses and novel therapeutic interventions for neurotropic viral infections.
Collapse
Affiliation(s)
- Rachel E McMillan
- Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, United States of America; Department of Pathology and Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States of America
| | - Ellen Wang
- Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States of America; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093, United States of America
| | - Aaron F Carlin
- Department of Pathology and Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States of America.
| | - Nicole G Coufal
- Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States of America; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093, United States of America.
| |
Collapse
|
|
16
|
Maher L, Aziz R. Always consider the travel history: West Nile virus infection presenting in rural Ireland. Br J Hosp Med (Lond) 2023; 84:1-2. [PMID: 36708336 DOI: 10.12968/hmed.2022.0314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Liam Maher
- Department of Internal Medicine, Bantry General Hospital, Cork, Ireland.,Department of General Medicine, Bantry General Hospital, Cork, Ireland
| | - Rizwan Aziz
- Department of General Medicine, Bantry General Hospital, Cork, Ireland
| |
Collapse
|
|
17
|
Rocamonde B, Hasan U, Mathieu C, Dutartre H. Viral-induced neuroinflammation: Different mechanisms converging to similar exacerbated glial responses. Front Neurosci 2023; 17:1108212. [PMID: 36937670 PMCID: PMC10017484 DOI: 10.3389/fnins.2023.1108212] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 02/10/2023] [Indexed: 03/06/2023] Open
Abstract
There is increasing evidence that viral infections are the source/origin of various types of encephalitis, encephalomyelitis, and other neurological and cognitive disorders. While the involvement of certain viruses, such as the Nipah virus and measles virus, is known, the mechanisms of neural invasion and the factors that trigger intense immune reactions are not fully understood. Based on recent publications, this review discusses the role of the immune response, interactions between viruses and glial cells, and cytokine mediators in the development of inflammatory diseases in the central nervous system. It also highlights the significant gaps in knowledge regarding these mechanisms.
Collapse
Affiliation(s)
- Brenda Rocamonde
- Centre International de Recherche en Infectiologie, Équipe d’Oncogenèse Rétrovirale, INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR 5308, École Normale Supérieure de Lyon, Université Lyon, Lyon, France
- Equipe Labellisée par la Fondation pour la Recherche Médicale, Labex Ecofect, Lyon, France
- *Correspondence: Brenda Rocamonde,
| | - Uzma Hasan
- Centre International de Recherche en Infectiologie, Team Enveloped Viruses, Vectors and Immunotherapy INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR 5308, École Normale Supérieure de Lyon, Université Lyon, Lyon, France
- The Lyon Immunotherapy for Cancer Laboratory (LICL), Centre de Recherche en Cancérologie de Lyon (CRCL, UMR INSERM 1052 – CNRS 5286) Centre Léon Bérard, Lyon, France
| | - Cyrille Mathieu
- Centre International de Recherche en Infectiologie Équipe Neuro-Invasion, Tropism and Viral Encephalitis, INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR 5308, École Normale Supérieure de Lyon, Université Lyon, Lyon, France
- Cyrille Mathieu,
| | - Hélène Dutartre
- Centre International de Recherche en Infectiologie, Équipe d’Oncogenèse Rétrovirale, INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR 5308, École Normale Supérieure de Lyon, Université Lyon, Lyon, France
- Equipe Labellisée par la Fondation pour la Recherche Médicale, Labex Ecofect, Lyon, France
- Hélène Dutartre,
| |
Collapse
|
|
18
|
Chauhan L, Matthews E, Piquet AL, Henao-Martinez A, Franco-Paredes C, Tyler KL, Beckham D, Pastula DM. Nervous System Manifestations of Arboviral Infections. CURRENT TROPICAL MEDICINE REPORTS 2022; 9:107-118. [PMID: 36124288 PMCID: PMC9476420 DOI: 10.1007/s40475-022-00262-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2022] [Indexed: 01/11/2023]
Abstract
Purpose of Review Complex environmental factors and human intervention influence the spread of arthropod vectors and the cycle of transmission of arboviruses. The spectrum of clinical manifestations is diverse, ranging from serious presentations like viral hemorrhagic fever (e.g., dengue, yellow fever, rift valley fever) or shock syndromes (e.g., dengue virus) to organ-specific illness like meningoencephalitis. Recent Findings A spectrum of clinical neurologic syndromes with potential acute devastating consequences or long-term sequelae may result from some arboviral infections. Summary In this review, we describe some of the most frequent and emerging neuro-invasive arboviral infections, spectrum of neurologic disorders including encephalitis, meningitis, myelitis or poliomyelitis, acute demyelinating encephalomyelitis, Guillain-Barré syndrome, and ocular syndromes.
Collapse
Affiliation(s)
- Lakshmi Chauhan
- Division of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045 USA
- Neuro-Infectious Diseases Group, Department of Neurology and Division of Infectious Diseases, University of Colorado, Anschutz Medical Center, Aurora, CO USA
| | - Elizabeth Matthews
- Neuro-Infectious Diseases Group, Department of Neurology and Division of Infectious Diseases, University of Colorado, Anschutz Medical Center, Aurora, CO USA
| | - Amanda L. Piquet
- Neuro-Infectious Diseases Group, Department of Neurology and Division of Infectious Diseases, University of Colorado, Anschutz Medical Center, Aurora, CO USA
| | - Andrés Henao-Martinez
- Division of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045 USA
| | - Carlos Franco-Paredes
- Division of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045 USA
- Hospital Infantil de México, Federico Gómez, México City, México
| | - Kenneth L. Tyler
- Division of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045 USA
- Neuro-Infectious Diseases Group, Department of Neurology and Division of Infectious Diseases, University of Colorado, Anschutz Medical Center, Aurora, CO USA
- Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Center, Aurora, CO USA
| | - David Beckham
- Division of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045 USA
- Neuro-Infectious Diseases Group, Department of Neurology and Division of Infectious Diseases, University of Colorado, Anschutz Medical Center, Aurora, CO USA
- Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Center, Aurora, CO USA
| | - Daniel M. Pastula
- Neuro-Infectious Diseases Group, Department of Neurology and Division of Infectious Diseases, University of Colorado, Anschutz Medical Center, Aurora, CO USA
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO USA
| |
Collapse
|
|
19
|
Milhim BHGA, da Rocha LC, Terzian ACB, Mazaro CCP, Augusto MT, Luchs A, Zini N, Sacchetto L, dos Santos BF, Garcia PHC, Rocha RS, Liso E, Brienze VMS, da Silva GCD, Vasilakis N, Estofolete CF, Nogueira ML. Arboviral Infections in Neurological Disorders in Hospitalized Patients in São José do Rio Preto, São Paulo, Brazil. Viruses 2022; 14:1488. [PMID: 35891468 PMCID: PMC9323204 DOI: 10.3390/v14071488] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 07/03/2022] [Accepted: 07/05/2022] [Indexed: 02/04/2023] Open
Abstract
Arbovirus infections are increasingly important causes of disease, whose spectrum of neurological manifestations are not fully known. This study sought to retrospectively assess the incidence of arboviruses in cerebrospinal fluid samples of patients with neurological symptoms to inform diagnosis of central and peripheral nervous system disorders. A total of 255 cerebrospinal fluid (CSF) samples collected from January 2016 to December 2017 were tested for dengue virus (DENV 1-4), Zika virus (ZIKV), and Chikungunya virus (CHIKV) in addition to other neurotropic arboviruses of interest, using genetic and serologic assays. Of the 255 CSF samples analyzed, 3.53% (09/255) were positive for arboviruses presenting mainly as meningitis, encephalitis, and cerebrovascular events, of which ZIKV was detected in 2.74% (7/255), DENV in 0.78% (2/255), in addition to an identified ILHV infection that was described previously. All the cases were detected in adults aged 18 to 74 years old. Our findings highlight the scientific and clinical importance of neurological syndromes associated with arboviruses and demonstrate the relevance of specific laboratory methods to achieve accurate diagnoses as well as highlight the true dimension of these diseases to ultimately improve public health planning and medical case management.
Collapse
Affiliation(s)
- Bruno H. G. A. Milhim
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Leonardo C. da Rocha
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Ana C. B. Terzian
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
- Laboratório de Imunologia Celular e Molecular (LICM), Avenida Augusto de Lima, 1715, Centro, Belo Horizonte 30190-002, MG, Brazil
- Instituto René Rachou Fundação Oswaldo Cruz, Avenida Augusto de Lima, 1715, Centro, Belo Horizonte 30190-002, MG, Brazil
| | - Carolina C. P. Mazaro
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Marcos T. Augusto
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Adriana Luchs
- Enteric Disease Laboratory, Department of Virology, Adolfo Lutz Institute, Avenida Dr. Arnaldo, 355, São Paulo 01246-902, SP, Brazil;
| | - Nathalia Zini
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Livia Sacchetto
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Barbara F. dos Santos
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Pedro H. C. Garcia
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Rodrigo S. Rocha
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Elisabete Liso
- Hospital de Base, Avenida Brigadeiro Faria Lima, 5544-Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (E.L.); (V.M.S.B.)
| | - Vânia M. S. Brienze
- Hospital de Base, Avenida Brigadeiro Faria Lima, 5544-Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (E.L.); (V.M.S.B.)
| | - Gislaine C. D. da Silva
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Nikos Vasilakis
- Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609, USA;
- Department of Preventive Medicine and Population Health, The University of Texas Medical Branch, Galveston, TX 77555-1150, USA
- Center for Vector-Borne and Zoonotic Diseases, The University of Texas Medical Branch, Galveston, TX 77555-0609, USA
- Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609, USA
- Center for Tropical Diseases, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609, USA
- Institute for Human Infection and Immunity, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0610, USA
| | - Cássia F. Estofolete
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
| | - Maurício L. Nogueira
- Laboratório de Pesquisas em Virologia [LPV], Faculdade de Medicina de São José do Rio Preto [FAMERP], Avenida Brigadeiro Faria Lima, 5544, Vila São Jose, São José do Rio Preto 15090-000, SP, Brazil; (B.H.G.A.M.); (L.C.d.R.); (A.C.B.T.); (C.C.P.M.); (M.T.A.); (N.Z.); (L.S.); (B.F.d.S.); (P.H.C.G.); (R.S.R.); (G.C.D.d.S.); (C.F.E.)
- Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609, USA;
| |
Collapse
|
|
20
|
Lino A, Erickson TA, Nolan MS, Murray KO, Ronca SE. A Preliminary Study of Proinflammatory Cytokines and Depression Following West Nile Virus Infection. Pathogens 2022; 11:pathogens11060650. [PMID: 35745504 PMCID: PMC9230011 DOI: 10.3390/pathogens11060650] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 01/25/2023] Open
Abstract
West Nile virus (WNV) is a neurotropic flavivirus that can cause acute febrile illness leading to neuroinvasive disease. Depression is a well-described outcome following infection, but the underlying pathogenic mechanisms are unknown. Proinflammatory cytokines play important roles in WNV infection, but their role in depression post-WNV remains unstudied. This research aimed to retrospectively evaluate associations between proinflammatory cytokines and new onset depression in a WNV cohort. Participants with asymptomatic WNV infection were significantly less likely to report new onset depression when compared to those with symptomatic disease. Participants with encephalitis and obesity were significantly more likely to report new onset depression post-infection. Based on univariate analysis of 15 antiviral or proinflammatory cytokines, depression was associated with elevated MCP-1 and decreased TNFα, whereas G-CSF was significantly elevated in those with a history of neuroinvasive WNV. However, no cytokines were statistically significant after adjusting for multiple comparisons using the Bonferroni method. While symptomatic WNV infection, encephalitis, and obesity were associated with new onset depression following infection, the role of proinflammatory cytokines requires additional studies. Further research involving paired acute-convalescent samples, larger sample sizes, and additional data points would provide additional insight into the impact of the inflammatory response on WNV-mediated depression.
Collapse
Affiliation(s)
- Allison Lino
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
| | - Timothy A. Erickson
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
| | - Melissa S. Nolan
- Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA;
| | - Kristy O. Murray
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
- Correspondence: (K.O.M.); (S.E.R.)
| | - Shannon E. Ronca
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
- Correspondence: (K.O.M.); (S.E.R.)
| |
Collapse
|
|
21
|
Choutka J, Jansari V, Hornig M, Iwasaki A. Unexplained post-acute infection syndromes. Nat Med 2022; 28:911-923. [PMID: 35585196 DOI: 10.1038/s41591-022-01810-6] [Citation(s) in RCA: 306] [Impact Index Per Article: 102.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 04/01/2022] [Indexed: 02/06/2023]
Abstract
SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.
Collapse
Affiliation(s)
- Jan Choutka
- Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czech Republic.
| | - Viraj Jansari
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
| | - Mady Hornig
- Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA
| | - Akiko Iwasaki
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. .,Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. .,Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA. .,Howard Hughes Medical Institute, Chevy Chase, MD, USA.
| |
Collapse
|
|
22
|
Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes. Pathogens 2022; 11:pathogens11010052. [PMID: 35056000 PMCID: PMC8779330 DOI: 10.3390/pathogens11010052] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/17/2021] [Accepted: 12/30/2021] [Indexed: 11/26/2022] Open
Abstract
West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.
Collapse
|
|
23
|
Damiano RF, Guedes BF, de Rocca CC, de Pádua Serafim A, Castro LHM, Munhoz CD, Nitrini R, Filho GB, Miguel EC, Lucchetti G, Forlenza O. Cognitive decline following acute viral infections: literature review and projections for post-COVID-19. Eur Arch Psychiatry Clin Neurosci 2022; 272:139-154. [PMID: 34173049 PMCID: PMC8231753 DOI: 10.1007/s00406-021-01286-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 06/21/2021] [Indexed: 12/15/2022]
Abstract
Recently, much attention has been drawn to the importance of the impact of infectious disease on human cognition. Several theories have been proposed, to explain the cognitive decline following an infection as well as to understand better the pathogenesis of human dementia, especially Alzheimer's disease. This article aims to review the state of the art regarding the knowledge about the impact of acute viral infections on human cognition, laying a foundation to explore the possible cognitive decline followed coronavirus disease 2019 (COVID-19). To reach this goal, we conducted a narrative review systematizing six acute viral infections as well as the current knowledge about COVID-19 and its impact on human cognition. Recent findings suggest probable short- and long-term COVID-19 impacts in cognition, even in asymptomatic individuals, which could be accounted for by direct and indirect pathways to brain dysfunction. Understanding this scenario might help clinicians and health leaders to deal better with a wave of neuropsychiatric issues that may arise following COVID-19 pandemic as well as with other acute viral infections, to alleviate the cognitive sequelae of these infections around the world.
Collapse
Affiliation(s)
- Rodolfo Furlan Damiano
- Departamento E Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, SP, 05403-903, Brazil.
| | - Bruno F. Guedes
- Department of Neurology, University of São Paulo, São Paulo, Brazil
| | - Cristiana Castanho de Rocca
- Departamento E Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, SP 05403-903 Brazil
| | - Antonio de Pádua Serafim
- Departamento E Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, SP 05403-903 Brazil
| | | | - Carolina Demarchi Munhoz
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Ricardo Nitrini
- Department of Neurology, University of São Paulo, São Paulo, Brazil
| | - Geraldo Busatto Filho
- Departamento E Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, SP 05403-903 Brazil
| | - Eurípedes Constantino Miguel
- Departamento E Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, SP 05403-903 Brazil
| | - Giancarlo Lucchetti
- Department of Medicine, Federal University of Juiz de Fora, Juiz de Fora, Brazil
| | - Orestes Forlenza
- Departamento E Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos, 785, Cerqueira César, São Paulo, SP 05403-903 Brazil
| |
Collapse
|
|
24
|
Bohmwald K, Andrade CA, Gálvez NMS, Mora VP, Muñoz JT, Kalergis AM. The Causes and Long-Term Consequences of Viral Encephalitis. Front Cell Neurosci 2021; 15:755875. [PMID: 34916908 PMCID: PMC8668867 DOI: 10.3389/fncel.2021.755875] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/01/2021] [Indexed: 12/15/2022] Open
Abstract
Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.
Collapse
Affiliation(s)
- Karen Bohmwald
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Catalina A Andrade
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Nicolás M S Gálvez
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Valentina P Mora
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - José T Muñoz
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Alexis M Kalergis
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| |
Collapse
|
|
25
|
Wang C, Wang L, Gu Y. Microglia, synaptic dynamics and forgetting. Brain Res Bull 2021; 174:173-183. [PMID: 34129917 DOI: 10.1016/j.brainresbull.2021.06.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 01/08/2023]
Abstract
Microglia are the major immune cells in the brain parenchyma. Besides their immune functions, microglia are important in regulating the dynamics of synapses. It is believed that the stability of synapses is essential for long-term storage and retrieval of memories, whereas microglial regulation of synaptic dynamics could affect the stability of memories, thus providing a potential mechanism for forgetting. In this review, we focus on the regulation of synaptic dynamics by microglia, as well as the subsequent effects on memory and forgetting, under physiological and pathological conditions. Revealing microglial regulation of synaptic dynamics will not only illuminate the physiological functions of microglia in the brain, but also provide us a new perspective to study the molecular and cellular mechanisms underlying forgetting. In addition, this will also improve our understanding of the process of memory encoding, storage and retrieval in the brain. Furthermore, uncovering the mechanisms through which microglia act on synaptic dynamics in pathological conditions will provide new strategies for the prevention and treatment of memory impairment in diseases.
Collapse
Affiliation(s)
- Chao Wang
- Center of Stem Cell and Regenerative Medicine, Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Lang Wang
- Department of Neurology of the First Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, Hangzhou, 310029, China
| | - Yan Gu
- Center of Stem Cell and Regenerative Medicine, Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
| |
Collapse
|
|
26
|
Koch M, Pozsgai É, Soós V, Nagy A, Girán J, Nyisztor N, Martyin T, Müller Z, Fehér M, Hajdú E, Varga C. Identifying risks for severity of neurological symptoms in Hungarian West Nile virus patients. BMC Infect Dis 2021; 21:65. [PMID: 33441090 PMCID: PMC7805165 DOI: 10.1186/s12879-020-05760-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/30/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND West Nile virus (WNV) infections have become increasingly prevalent in certain European countries, including Hungary. Although most human infections do not cause severe symptoms, in approximately 1% of cases WNV infections can lead to severe WNV neuroinvasive disease (WNND) and death. The goal of our study was to assess the neurological status changes of WNV -infected patients admitted to inpatient care and to identify potential risk factors as underlying reasons for severe neurological outcome. METHODS We conducted a retrospective chart review of 66 WNV-infected patients from four Hungarian medical centers. Patients' neurological status at hospital admission and at two follow-up intervals (1st follow-up, within 60-90 days and 2nd follow-up, within 150-180 days, after hospital discharge) were assessed. All of the 66 patients in the initial sample had some type of neurological symptoms and 56 patients were diagnosed with WNND. The modified Rankin Scale (mRS) and the West Nile Virus Neurological Index (WNV-N Index), a scoring system designed for the purpose of this study, were used for neurological status assessment. Patients were dichotomized into two categories, "moderately severe" and "severe" based on their neurological status. Descriptive analysis for sample description, stratified analysis for calculation of odds ratio (OR) and logistic regression for continuous input variables, were performed. RESULTS The average number of days between the onset of neurological symptoms and hospital admission (the neurological symptom interval) was 6.01 days. Complications during the hospital stay arose in almost a fifth of the patients (18.2%) and 5 patients died. Each day's increase in the neurological symptom interval significantly increased the risk for developing a severe neurological status following hospital admission (0.799-fold and 0.688-fold, based on the WNV-N Index and mRS, respectively). Patients' age, comorbidity, presence of complications and symptoms of malaise, and gait uncertainty were shown to be independent risk factors for severe neurological status. CONCLUSIONS Timely hospital admission of patients with neurological symptoms as well as risk assessment by clinicians - possibly with an optimal assessment tool for estimating neurological status- could improve the neurological outcome of WNV-infected patients.
Collapse
Affiliation(s)
- Márton Koch
- Department of Emergency Medicine, Somogy County Kaposi Mór Teaching Hospital, Tallián Gyula Street, 20-32, Kaposvár, 7400 Hungary
| | - Éva Pozsgai
- Department of Public Health, Medical School, University of Pécs, Szigeti Street, 12, Pécs, 7624 Hungary
- Institute of Primary Health Care, Medical School, University of Pécs, Rákóczi Street 2, Pécs, 7623 Hungary
| | - Viktor Soós
- Department of Emergency Medicine, Somogy County Kaposi Mór Teaching Hospital, Tallián Gyula Street, 20-32, Kaposvár, 7400 Hungary
| | - Anna Nagy
- National Reference Laboratory for Viral Zoonoses; National Public Health Center, 1097 Albert Flórián Road 2-6, Budapest, Hungary
| | - János Girán
- Department of Public Health, Medical School, University of Pécs, Szigeti Street, 12, Pécs, 7624 Hungary
| | - Norbert Nyisztor
- Department of Infectious Diseases (Hepatology and Immunology), Békés County Central Hospital, Semmelweis Street 1, Gyula, 5700 Hungary
| | - Tibor Martyin
- Department of Infectious Diseases (Hepatology and Immunology), Békés County Central Hospital, Semmelweis Street 1, Gyula, 5700 Hungary
| | - Zsófia Müller
- Department of Infectious Diseases, Fejér County St George Teaching Hospital, Seregélyesi Street 3, Székesfehérvár, 8000 Hungary
| | - Melánia Fehér
- Department of Infectious Diseases, Fejér County St George Teaching Hospital, Seregélyesi Street 3, Székesfehérvár, 8000 Hungary
| | - Edit Hajdú
- Department of Infectology, University of Szeged, Albert Szent-Györgyi Health Center, Kálvária Avenue 57, Szeged, 6725 Hungary
| | - Csaba Varga
- Department of Emergency Medicine, Somogy County Kaposi Mór Teaching Hospital, Tallián Gyula Street, 20-32, Kaposvár, 7400 Hungary
- Institute of Emergency Care and Pedagogy of Health, Faculty of Health Sciences, University of Pécs, Vörösmarty Mihály Street 4, Pécs, 7621 Hungary
| |
Collapse
|
|
27
|
Stonedahl S, Clarke P, Tyler KL. The Role of Microglia during West Nile Virus Infection of the Central Nervous System. Vaccines (Basel) 2020; 8:E485. [PMID: 32872152 PMCID: PMC7563127 DOI: 10.3390/vaccines8030485] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 08/22/2020] [Accepted: 08/26/2020] [Indexed: 12/28/2022] Open
Abstract
Encephalitis resulting from viral infections is a major cause of hospitalization and death worldwide. West Nile Virus (WNV) is a substantial health concern as it is one of the leading causes of viral encephalitis in the United States today. WNV infiltrates the central nervous system (CNS), where it directly infects neurons and induces neuronal cell death, in part, via activation of caspase 3-mediated apoptosis. WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. Microglia are the resident immune cells of the brain and monitor the CNS for signs of injury or pathogens. Following infection with WNV, microglia exhibit a change in morphology consistent with activation and are associated with increased expression of proinflammatory cytokines. Recent research has focused on deciphering the role of microglia during WNV encephalitis. Microglia play a protective role during infections by limiting viral growth and reducing mortality in mice. However, it also appears that activated microglia are triggered by T cells to mediate synaptic elimination at late times during infection, which may contribute to long-term neurological deficits following a neuroinvasive WNV infection. This review will discuss the important role of microglia in the pathogenesis of a neuroinvasive WNV infection. Knowledge of the precise role of microglia during a WNV infection may lead to a greater ability to treat and manage WNV encephalitis.
Collapse
Affiliation(s)
- Sarah Stonedahl
- Department of Immunology and Microbiology University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
| | - Penny Clarke
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Kenneth L. Tyler
- Department of Immunology and Microbiology, Infectious Disease, Medicine and Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Department of Veterans Affairs, Aurora, CO 80045, USA
| |
Collapse
|
|
28
|
Clé M, Eldin P, Briant L, Lannuzel A, Simonin Y, Van de Perre P, Cabié A, Salinas S. Neurocognitive impacts of arbovirus infections. J Neuroinflammation 2020; 17:233. [PMID: 32778106 PMCID: PMC7418199 DOI: 10.1186/s12974-020-01904-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 07/17/2020] [Indexed: 12/15/2022] Open
Abstract
Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.
Collapse
Affiliation(s)
- Marion Clé
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, France
| | - Patrick Eldin
- Institute of Research in Infectiology of Montpellier, CNRS, University of Montpellier, Montpellier, France
| | - Laurence Briant
- Institute of Research in Infectiology of Montpellier, CNRS, University of Montpellier, Montpellier, France
| | - Annie Lannuzel
- Neurology Unit, INSERM CIC 1424, Guadeloupe University Hospital, Université des Antilles, Pointe-à-Pitre, Guadeloupe, France
- INSERM U1127, CNRS, UMR7225, Brain and Spine Institute, Sorbonne University Medical School, Paris, France
| | - Yannick Simonin
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, France
| | - Philippe Van de Perre
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, CHU Montpellier, Montpellier, France
| | - André Cabié
- INSERM CIC 1424, Infectious Disease and Tropical Medicine Unit, Martinique University Hospital, Université des Antilles EA4537, Martinique, France.
| | - Sara Salinas
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, France.
| |
Collapse
|
|
29
|
West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and "One Health" Implications. Pathogens 2020; 9:pathogens9070589. [PMID: 32707644 PMCID: PMC7400489 DOI: 10.3390/pathogens9070589] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/16/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
West Nile virus (WNV) is an important zoonotic flavivirus responsible for mild fever to severe, lethal neuroinvasive disease in humans, horses, birds, and other wildlife species. Since its discovery, WNV has caused multiple human and animal disease outbreaks in all continents, except Antarctica. Infections are associated with economic losses, mainly due to the cost of treatment of infected patients, control programmes, and loss of animals and animal products. The pathogenesis of WNV has been extensively investigated in natural hosts as well as in several animal models, including rodents, lagomorphs, birds, and reptiles. However, most of the proposed pathogenesis hypotheses remain contentious, and much remains to be elucidated. At the same time, the unavailability of specific antiviral treatment or effective and safe vaccines contribute to the perpetuation of the disease and regular occurrence of outbreaks in both endemic and non-endemic areas. Moreover, globalisation and climate change are also important drivers of the emergence and re-emergence of the virus and disease. Here, we give an update of the pathobiology, epidemiology, diagnostics, control, and “One Health” implications of WNV infection and disease.
Collapse
|
|
30
|
Long-term, West Nile virus-induced neurological changes: A comparison of patients and rodent models. Brain Behav Immun Health 2020; 7:100105. [PMID: 34589866 PMCID: PMC8474605 DOI: 10.1016/j.bbih.2020.100105] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/07/2020] [Accepted: 07/12/2020] [Indexed: 02/06/2023] Open
Abstract
West Nile virus (WNV) is a mosquito-borne virus that can cause severe neurological disease in those infected. Those surviving infection often present with long-lasting neurological changes that can severely impede their lives. The most common reported symptoms are depression, memory loss, and motor dysfunction. These sequelae can persist for the rest of the patients’ lives. The pathogenesis behind these changes is still being determined. Here, we summarize current findings in human cases and rodent models, and discuss how these findings indicate that WNV induces a state in the brain similar neurodegenerative diseases. Rodent models have shown that infection leads to persistent virus and inflammation. Initial infection in the hippocampus leads to neuronal dysfunction, synapse elimination, and astrocytosis, all of which contribute to memory loss, mimicking findings in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). WNV infection acts on pathways, such as ubiquitin-signaled protein degradation, and induces the production of molecules, including IL-1β, IFN-γ, and α-synuclein, that are associated with neurodegenerative diseases. These findings indicate that WNV induces neurological damage through similar mechanisms as neurodegenerative diseases, and that pursuing research into the similarities will help advance our understanding of the pathogenesis of WNV-induced neurological sequelae.
In patients with and without diagnosed WNND, there are long-lasting neurological sequelae that can mimic neurodegenerative diseases. Some rodent models of WNV reproduce some of these changes with mechanisms similar to neurodegenerative diseases. There is significant overlap between WNV and ND pathogenesis and this has been understudied. Further research needs to be done to determine accuracy of animal models compared to human patients.
Collapse
|
|
31
|
Abstract
PURPOSE OF REVIEW The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated. RECENT FINDINGS The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific. SUMMARY T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.
Collapse
Affiliation(s)
| | - Robyn S. Klein
- Departments of Medicine
- Pathology and Immunology
- Neurosciences Washington University School of Medicine, St. Louis, Missouri, USA
| |
Collapse
|
|
32
|
Retrospective Descriptive Analysis of West Nile Neuroinvasive Disease (WNND) in Northwest Louisiana. Int J Microbiol 2020; 2020:3513859. [PMID: 32454831 PMCID: PMC7231183 DOI: 10.1155/2020/3513859] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 03/08/2020] [Accepted: 03/13/2020] [Indexed: 11/30/2022] Open
Abstract
Aims The aim of the study was to describe the presentation characteristics and epidemiology of WNND in Louisiana to improve future recognition of cases and decrease inappropriate antibiotic use. Settings and Design. It was a retrospective descriptive-analytic cohort study. A total of 23 patients with WNND were identified at one tertiary care hospital center in Northwest Louisiana from a retrospective chart review from January 1, 2012 to October 31, 2017. Results The median age was 49 years (range: 15–75) for patients with WNND. Of 23 patients diagnosed with WNND, twelve (52%) were diagnosed with encephalitis (WNE), six (26%) were diagnosed with meningitis (WNM), and five (22%) with myelitis (WNME). The common symptoms with WNND were fever in 65%, altered mental status in 61%, headache in 52%, fatigue in 43%, gastrointestinal symptoms in 43%, rigors in 30%, imbalance in 26%, rash in 9%, and seizures in 26% of patients. Most patients presented in the late summer season. The average duration of antibiotics given was six days. The average number of days from the admission to the diagnosis of WNND was nine days (3 to 16 days). Twenty-one (91%) patients survived the infection. Conclusions Identifying WNV infection early in its clinical course would help in decreasing inappropriate antibiotic use when patients presented with fever and meningeal symptoms. Performing WNV serology in CSF studies is critical in making the diagnosis.
Collapse
|
|
33
|
Gnann JW, Agrawal A, Hart J, Buitrago M, Carson P, Hanfelt-Goade D, Tyler K, Spotkov J, Freifeld A, Moore T, Reyno J, Masur H, Jester P, Dale I, Li Y, Aban I, Lakeman FD, Whitley RJ. Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease. Emerg Infect Dis 2020; 25:2064-2073. [PMID: 31625835 PMCID: PMC6810207 DOI: 10.3201/eid2511.190537] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Immunoglobulin administered to adults with neuroinvasive disease appeared to be safe but was not demonstrated to improve clinical outcomes. West Nile Virus (WNV) can result in clinically severe neurologic disease. There is no treatment for WNV infection, but administration of anti-WNV polyclonal human antibody has demonstrated efficacy in animal models. We compared Omr-IgG-am, an immunoglobulin product with high titers of anti-WNV antibody, with intravenous immunoglobulin (IVIG) and normal saline to assess safety and efficacy in patients with WNV neuroinvasive disease as part of a phase I/II, randomized, double-blind, multicenter study in North America. During 2003–2006, a total of 62 hospitalized patients were randomized to receive Omr-IgG-am, standard IVIG, or normal saline (3:1:1). The primary endpoint was medication safety. Secondary endpoints were morbidity and mortality, measured using 4 standardized assessments of cognitive and functional status. The death rate in the study population was 12.9%. No significant differences were found between groups receiving Omr-IgG-am compared with IVIG or saline for either the safety or efficacy endpoints.
Collapse
|
|
34
|
Vittor AY, Long M, Chakrabarty P, Aycock L, Kollu V, DeKosky ST. West Nile Virus-Induced Neurologic Sequelae-Relationship to Neurodegenerative Cascades and Dementias. CURRENT TROPICAL MEDICINE REPORTS 2020; 7:25-36. [PMID: 32775145 DOI: 10.1007/s40475-020-00200-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Purpose of Review West Nile virus (WNV) emerged from Central Africa in the 1990s and is now endemic throughout much of the world. Twenty years after its introduction in the USA, it is becoming apparent that neurological impairments can persist for years following infection. Here, we review the epidemiological data in support of such long-term deficits and discuss possible mechanisms that drive these persistent manifestations. Recent Findings Focusing on the recently discovered antimicrobial roles of amyloid and alpha-synuclein, we connect WNV late pathology to overlapping features encountered in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. We also summarize new research on microglial activation and engulfment of neural synapses seen in recovered WNV as well as in neurodegenerative diseases, and discuss how loss of integrity of the blood-brain barrier (BBB) may exacerbate this process. Summary Neuroinvasive viral infections such as WNV may be linked epidemiologically and mechanistically to neurodegeneration. This may open doors to therapeutic options for hitherto untreatable infectious sequelae; additionally, it may also shed light on the possible infectious etiologies of age-progressive neurodegenerative dementias.
Collapse
Affiliation(s)
- Amy Y Vittor
- Division of Infectious Disease and Global Medicine, University of Florida, Gainesville, FL, USA
| | - Maureen Long
- College of Veterinary Medicine, Department of Comparative, Diagnostic, and Population Medicine, University of Florida, Gainesville, FL, USA
| | - Paramita Chakrabarty
- Department of Neuroscience, Center for Translational Research in Neurodegenerative Diseases, and McKnight Brain Institute, University of Florida, Gainesville, FL, USA
| | - Lauren Aycock
- School of Medicine, University of Florida, Gainesville, FL, USA
| | - Vidya Kollu
- Division of Infectious Disease and Global Medicine, University of Florida, Gainesville, FL, USA
| | - Steven T DeKosky
- Department of Neurology and McKnight Brain Institute, University of Florida, Gainesville, FL, USA
| |
Collapse
|
|
35
|
Karaba AH, Blair PW, Martin K, Saheed MO, Carroll KC, Borowitz MJ. The Effects of a Systemwide Diagnostic Stewardship Change on West Nile Virus Disease Ordering Practices. Open Forum Infect Dis 2019; 6:ofz488. [PMID: 32128331 PMCID: PMC7047944 DOI: 10.1093/ofid/ofz488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 11/13/2019] [Indexed: 11/23/2022] Open
Abstract
We report that removing the clinically insensitive West Nile virus CSF nucleic acid amplification test (NAAT) from the electronic health record (EHR) test. This diagnostic stewardship intervention decreased costs and may have improved diagnostic yield.
Collapse
Affiliation(s)
- Andrew H Karaba
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Paul W Blair
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Austere Environments Consortium for Enhanced Sepsis Outcomes, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland
| | - Kevin Martin
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mustapha O Saheed
- Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Karen C Carroll
- Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michael J Borowitz
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
36
|
Abstract
BACKGROUND Data to guide neurointensivists seeing patients with West Nile Neuroinvasive disease (WNND) are lacking. We present a comparatively large series of patients with WNND admitted to the intensive care unit (ICU) and provide data on their early diagnosis, triage to the ICU and predictors of short-term outcomes. METHODS We retrospectively identified patients aged ≥ 18 years old with WNND from January 1999 to November 2016. Demographic and clinical data, the modified Rankin Scale at discharge and disposition were collected. Univariate analysis was performed to find predictors of ICU admission and to assess the impact of ICU admission on the short-term outcomes. P values < 0.05 were considered significant. RESULTS Among 26 patients, 16 were admitted to the ICU. Age < 60 years and the presentation with encephalitis and acute flaccid paralysis predicted ICU admission (P = 0.044 and 0.0007). Among patients requiring ICU admission, four died and no one was discharged home. ICU admission predicted longer hospital stay (P = 0.021), inhospital death (P = 0.034), survival with inability to walk independently (P = 0.0094), and discharge disposition other than home (P = 0.007). In the ICU group, older age was associated with longer hospital stay (P = 0.0001) and inhospital death (P = 0.035). CONCLUSION WNND requiring ICU care has a high morbidity and mortality, especially among older patients. Survivors are highly disabled at discharge, but many improve over time. Therefore, more data on the long-term prognosis of survivors are needed to guide the goals of care in the acute setting.
Collapse
Affiliation(s)
- Maximiliano A Hawkes
- Division of Critical Care Neurology, Department of Neurology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA.
| | - Ivan D Carabenciov
- Division of Critical Care Neurology, Department of Neurology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA
| | - Eelco F M Wijdicks
- Division of Critical Care Neurology, Department of Neurology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA
| | - Alejandro A Rabinstein
- Division of Critical Care Neurology, Department of Neurology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA
| |
Collapse
|
|
37
|
Abstract
OBJECTIVE To assess the long-term outcomes of patients hospitalized with severe West Nile neuroinvasive disease. DESIGN Retrospective cohort. SETTING Patients admitted to a referral center (Saint Mary's Hospital, Mayo Clinic). PARTICIPANTS Twenty-six patients with West Nile neuroinvasive disease were identified by retrospective search of electronic database of Saint Mary's Hospital from January 1999 to November 2016. INTERVENTIONS Retrospective electronic medical records review and prospective telephone follow-up. MEASUREMENTS AND MAIN RESULTS Functional disability and cognitive outcomes were evaluated with the modified Rankin Scale and the Telephone Interview for Cognitive Status scores. Data on the time that the patient returned home after the hospitalization for West Nile neuroinvasive disease and the time of return to work were also collected. We identified 26 patients (81% males), 59 ± 17 years old. After a median hospital stay of 14.5 days (3-126), four patients died and 90% of survivors had a modified Rankin Scale of 3-5. Two additional patients died, and 80% of survivors had a modified Rankin Scale of 0-2 after a median follow-up of 73 months (1-144). Seven patients had cognitive impairment, which was severe in two of them. The combination of encephalitis and acute flaccid paralysis at presentation was associated with lower likelihood of returning home within 1 month after discharge (p < 0.01). Patients who required mechanical ventilation were more likely to have a modified Rankin Scale of 3-5 at last follow-up (p = 0.03), less likely to return home within 1 month of discharge (p < 0.01), less likely to return to their jobs (p < 0.01), and showed a trend toward having cognitive impairment (p = 0.05). CONCLUSIONS Despite having poor outcomes at discharge, most West Nile neuroinvasive disease survivors with severe early disability can recover functional independence in the long term, justifying aggressive support during the acute phase and extensive rehabilitation efforts.
Collapse
|
|
38
|
Tisoncik-Go J, Gale M. Microglia in Memory Decline from Zika Virus and West Nile Virus Infection. Trends Neurosci 2019; 42:757-759. [PMID: 31495452 DOI: 10.1016/j.tins.2019.08.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 08/20/2019] [Indexed: 02/01/2023]
Abstract
Neurotropic viral infection can result in complications underscored by persistent T cell presence in the brain linked with cognitive decline. A recent study by Garber et al. showed that sustained T cell production of interferon (IFN)-γ mediating microglia activation triggers cognitive decline during recovery from Zika virus (ZIKV) or West Nile virus (WNV) infection.
Collapse
Affiliation(s)
- Jennifer Tisoncik-Go
- Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, USA; Department of Immunology, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA
| | - Michael Gale
- Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, USA; Department of Immunology, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
| |
Collapse
|
|
39
|
Yu A, Ferenczi E, Moussa K, Eliott D, Matiello M. Clinical Spectrum of West Nile Virus Neuroinvasive Disease. Neurohospitalist 2019; 10:43-47. [PMID: 31839864 DOI: 10.1177/1941874419868636] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
West Nile virus (WNV) is the most common arbovirus infection in the United States. The diagnosis requires consideration of not only a broad spectrum of presenting symptoms, ranging from a mild febrile illness to severe encephalitis and acute flaccid paralysis, but also public health risk factors and seasonality. There is no approved targeted therapy for WNV, so treatment relies on supportive care, management of neurologic sequelae and airway, treatment of other systems including the eye, and aggressive rehabilitation. Here, we describe a series of 3 cases of WNV encountered in September 2018 at one institution. First, we describe a case of WNV encephalitis with worsened dyskinesias and a relatively good recovery. Second, we describe a severe WNV encephalitis with overlying motor neuron involvement with a poor outcome. Finally, we describe a case of a WNV meningitis with significant bilateral chorioretinitis, an underappreciated complication of WNV infections. Through these cases, we review the epidemiology of WNV, risk factors for infection, the neurologic sequalae and long-term outcomes, and the importance of recognizing ocular involvement to prevent ophthalmologic complications.
Collapse
Affiliation(s)
- Andrew Yu
- Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| | - Emily Ferenczi
- Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| | - Kareem Moussa
- Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA
| | - Dean Eliott
- Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA
| | - Marcelo Matiello
- Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| |
Collapse
|
|
40
|
Castro-Jorge LAD, Siconelli MJL, Ribeiro BDS, Moraes FMD, Moraes JBD, Agostinho MR, Klein TM, Floriano VG, Fonseca BALD. West Nile virus infections are here! Are we prepared to face another flavivirus epidemic? Rev Soc Bras Med Trop 2019; 52:e20190089. [PMID: 30942263 DOI: 10.1590/0037-8682-0089-2018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 02/26/2019] [Indexed: 01/29/2023] Open
Abstract
Emerging arthropod-borne viruses (arboviruses), such as chikungunya and Zika viruses, are a major threat to public health in countries like Brazil where biodiversity is high and medical care is sometimes precarious. West Nile fever is a disease caused by the West Nile Virus (WNV), an RNA virus belonging to the Flaviviridae family. It is transmitted by infected mosquitoes to numerous animals like birds, reptiles and mammals, including human and non-human primates. In the last decade, the number of reported cases of WNV infection in humans and animals has increased in the Americas. Circulation of WNV in forests and rural areas in Brazil has been detected based on serological surveys and, in 2014, the first case of West Nile fever was confirmed in a patient from Piauí State. In 2018, the virus was isolated for the first time from a horse from a rural area in the state of Espírito Santo presenting with a neurological disorder; this raises the possibility that other cases of WNV encephalitis may have occurred without clinical recognition and without laboratory diagnosis by specific assays. The imminent WNV outbreak poses a challenge for Brazilian clinicians and researchers. In this review, we summarize the basic biological and ecological characteristics of this virus and the clinical presentation and treatment of febrile illnesses caused by WNV. We also discuss the epidemiological aspects, prophylaxis of WNV infections, and monitoring strategies that could be applied in the possibility of a WNV outbreak in Brazil.
Collapse
Affiliation(s)
- Luiza Antunes de Castro-Jorge
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Márcio Junio Lima Siconelli
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Beatriz Dos Santos Ribeiro
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Flávia Masson de Moraes
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Jonathan Ballico de Moraes
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Mayara Rovariz Agostinho
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Taline Monteiro Klein
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Vitor Gonçalves Floriano
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | | |
Collapse
|
|
41
|
Herring R, Desai N, Parnes M, Jarjour I. Pediatric West Nile Virus-Associated Neuroinvasive Disease: A Review of the Literature. Pediatr Neurol 2019; 92:16-25. [PMID: 30611518 DOI: 10.1016/j.pediatrneurol.2018.07.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 07/10/2018] [Accepted: 07/15/2018] [Indexed: 10/27/2022]
Abstract
Over the past two decades, West Nile virus has become the most common arbovirus in North America, leading to several outbreaks and infecting thousands of people. Mosquitos help transmit the virus in the majority of cases, but transmission occurs via blood transfusions, organ transplantation, and possibly pregnancy and breastfeeding. While most infected patients experience mild to no symptoms, thousands of West Nile virus-associated neuroinvasive cases have been reported in the United States, with over 700 cases occurring in children from 2003 to 2016. Neuroinvasive disease presents as meningitis, encephalitis, or acute flaccid paralysis, and carries a high likelihood of poor outcome, including severe neurological disability or death. To date, no pharmacologic treatment has proven effective. Therapeutic clinical trials have not been successfully completed due to the sporadic nature of viral outbreaks and resultant poor study enrollment. Although older age and chronic disease are risk factors for neuroinvasive West Nile virus disease in adults, the specific factors that influence the risk in pediatric populations have not been fully elucidated. This review summarizes the most recent literature regarding West Nile virus-associated neuroinvasive disease, especially as it pertains to the pediatric population. Moreover, the review describes the epidemiology, clinical, laboratory, and radiographic findings, and outlines the various therapies that have been trialed and potential future research directions.
Collapse
Affiliation(s)
- Rachelle Herring
- Section of Child Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.
| | - Nilesh Desai
- Section of Neuroradiology, Department of Radiology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
| | - Mered Parnes
- Section of Child Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
| | - Imad Jarjour
- Section of Child Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
| |
Collapse
|
|
42
|
Potokar M, Jorgačevski J, Zorec R. Astrocytes in Flavivirus Infections. Int J Mol Sci 2019; 20:ijms20030691. [PMID: 30736273 PMCID: PMC6386967 DOI: 10.3390/ijms20030691] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 01/27/2019] [Accepted: 01/29/2019] [Indexed: 12/14/2022] Open
Abstract
Virus infections of the central nervous system (CNS) can manifest in various forms of inflammation, including that of the brain (encephalitis) and spinal cord (myelitis), all of which may have long-lasting deleterious consequences. Although the knowledge of how different viruses affect neural cells is increasing, understanding of the mechanisms by which cells respond to neurotropic viruses remains fragmented. Several virus types have the ability to infect neural tissue, and astrocytes, an abundant and heterogeneous neuroglial cell type and a key element providing CNS homeostasis, are one of the first CNS cell types to get infected. Astrocytes are morphologically closely aligned with neuronal synapses, blood vessels, and ventricle cavities, and thereby have the capacity to functionally interact with neurons and endothelial cells. In this review, we focus on the responses of astrocytes to infection by neurotropic flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV), which have all been confirmed to infect astrocytes and cause multiple CNS defects. Understanding these mechanisms may help design new strategies to better contain and mitigate virus- and astrocyte-dependent neuroinflammation.
Collapse
Affiliation(s)
- Maja Potokar
- Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
- Celica BIOMEDICAL, Tehnološki park 24, 1000 Ljubljana, Slovenia.
| | - Jernej Jorgačevski
- Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
- Celica BIOMEDICAL, Tehnološki park 24, 1000 Ljubljana, Slovenia.
| | - Robert Zorec
- Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
- Celica BIOMEDICAL, Tehnološki park 24, 1000 Ljubljana, Slovenia.
| |
Collapse
|
|
43
|
Unger J, Jervis Rademeyer H, Furlan JC, Pujol C, Dawe J, Musselman KE. Personalized adapted locomotor training for an individual with sequelae of West Nile virus infection: a mixed-method case report. Physiother Theory Pract 2018; 36:844-854. [PMID: 30136877 DOI: 10.1080/09593985.2018.1510450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
BACKGROUND West Nile virus (WNV) can have severe consequences, including encephalitis and paralysis. Purpose: To describe the benefits of intensive locomotor training (LT) for an individual with a previous WNV infection resulting in chronic paraplegia. Case Description: The patient, who became a wheelchair user following standard rehabilitation, began LT 3 years post infection. Her goals included standing and walking with an assistive device and transferring independently. The intervention consisted of bodyweight-supported treadmill training and overground training, which involved walking, balancing, strengthening, and transferring activities. Outcomes: Following 5 months of LT, the patient ambulated independently with a walker at a speed = 0.34m/s. She walked 110.1 metres in 6 minutes and increased her Berg Balance Scale score by 17 points. These improvements were either maintained or further increased 3 months post LT. The patient's perspectives on LT were collected through a semi-structured interview. A conventional content analysis, which uses data to drive themes, revealed three themes: (1) recalibrating goals, (2) outcomes (i.e. physical and psychological benefits, such as a sense of accomplishment), and (3) challenges of LT and effective coping strategies. Conclusions: The patient demonstrated improved balance and walking abilities. Intensive LT was feasible and effective for this individual with chronic paraplegia due to WNV infection.
Collapse
Affiliation(s)
- Janelle Unger
- Lyndhurst Centre, Toronto Rehabilitation Institute-University Health Network , Toronto, ON, Canada.,Rehabilitation Sciences Institute, Faculty of Medicine, University of Toronto , Toronto, ON, Canada
| | - Hope Jervis Rademeyer
- Lyndhurst Centre, Toronto Rehabilitation Institute-University Health Network , Toronto, ON, Canada.,School of Physical Therapy, College of Medicine, University of Saskatchewan , Saskatoon, SK, Canada
| | - Julio C Furlan
- Lyndhurst Centre, Toronto Rehabilitation Institute-University Health Network , Toronto, ON, Canada.,Department of Medicine, Division of Physical Medicine and Rehabilitation, University of Toronto , Toronto, ON, Canada
| | - Clara Pujol
- Lyndhurst Centre, Toronto Rehabilitation Institute-University Health Network , Toronto, ON, Canada
| | - Jaclyn Dawe
- Lyndhurst Centre, Toronto Rehabilitation Institute-University Health Network , Toronto, ON, Canada.,Rehabilitation Sciences Institute, Faculty of Medicine, University of Toronto , Toronto, ON, Canada
| | - Kristin E Musselman
- Lyndhurst Centre, Toronto Rehabilitation Institute-University Health Network , Toronto, ON, Canada.,Rehabilitation Sciences Institute, Faculty of Medicine, University of Toronto , Toronto, ON, Canada.,School of Physical Therapy, College of Medicine, University of Saskatchewan , Saskatoon, SK, Canada.,Department of Physical Therapy, Faculty of Medicine, University of Toronto , Toronto, ON, Canada
| |
Collapse
|
|
44
|
Abstract
We aimed to describe the clinical characteristics of West Nile patients reported in Québec in 2012 and 2013 and to document physical, mental and functional status 24 months after symptom onset according to illness severity. The cases were recruited by a public health professional. Data were collected from public health files, medical records and two standardised phone questionnaires: the Short Form-36 and the Instrumental Activities of Daily Living. In all, 92 persons participated in the study (25 had West Nile fever (WNF), 18 had meningitis and 49 had encephalitis). Encephalitis participants were older, had more underlying medical conditions, more neurological symptoms, worse hospital course and higher lethality than meningitis or WNF participants. Nearly half of the surviving hospitalised encephalitis patients required extra support upon discharge. At 24-month follow-up, encephalitis and meningitis patients had a lower score in two domains of the mental component: mental health and social functioning (P = 0.0025 and 0.0297, respectively) compared with the norms based on age- and sex-matched Canadians. Physical status was not affected by West Nile virus (WNV) infection. In addition, 5/36 (15%) of encephalitis, 1/17 (6%) of meningitis and 1/23 (5%) of WNF participants had new functional limitations 24 months after symptom onset. In summary, mental and functional sequelae in encephalitis patients are likely to represent a source of long-term morbidity. Preventive measures should target patients at higher risk of severe illness after WNV infection.
Collapse
|
|
45
|
Abstract
The use of a mouse model to study the breadth of symptoms and disease severity seen in human West Nile virus (WNV) infection can provide insight into the kinetics of the immune response and the specific pathways responsible for control of WNV infection and viral clearance. Here, we provide protocols for performing WNV infection of mice, as well as complete immunophenotyping analysis of the cellular immune response to infection in both the periphery and the central nervous system in a mouse model of WNV infection. © 2017 by John Wiley & Sons, Inc.
Collapse
Affiliation(s)
- Jessica B Graham
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jessica L Swarts
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jennifer M Lund
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,Department of Global Health, University of Washington, Seattle, Washington
| |
Collapse
|
|
46
|
Yeung MW, Tomlinson G, Loeb M, Sander B. Health-related quality of life in persons with West Nile virus infection: a longitudinal cohort study. Health Qual Life Outcomes 2017; 15:210. [PMID: 29061146 PMCID: PMC5654088 DOI: 10.1186/s12955-017-0787-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 10/11/2017] [Indexed: 01/18/2023] Open
Abstract
Background West Nile virus (WNV) infections are predominantly asymptomatic, although almost 1% become neuroinvasive and debilitating. We describe the impact of neuroinvasive and non-neuroinvasive disease on patient health-related quality of life (HRQoL). Methods Short Form 36 questionnaire data came from a Canadian WNV cohort (Loeb 2008) of 154 patients followed for up to three years. We generated health utilities using the SF-6D. We calculated mean utility scores throughout follow-up and examined predictors using a linear mixed-effects model. We summarized HRQoL post-acute infection as: (i) long-term utility (mean of scores one year onward); (ii) area under the curve (AUC) one year onward. We examined predictors using beta regression. We used multiple imputation for sensitivity analysis. Results Mean utility scores improved from 0.59 (95% CI: 0.38, 0.93) at baseline to 0.77 (0.53, 1) at six months, before plateauing for the remaining two years. Mean long-term utility was 0.81 (0.78, 0.85) and mean AUC was 0.80 (0.76, 0.84). Patients with neuroinvasive disease had consistently worse scores than their non-neuroinvasive counterparts, with the gap nearly closed after six months. After adjusting for confounding, neuroinvasive disease was not a significant predictor of HRQoL either throughout follow-up or post-acute infection. Rather, number of comorbidities and baseline utility scores were. Sensitivity analysis showed similar findings. Conclusions Patients with WNV infection reported low HRQoL during acute illness, but improved rapidly by six months, regardless of neuroinvasive disease status. This is the first study reporting health utilities for WNV infection. Electronic supplementary material The online version of this article (10.1186/s12955-017-0787-5) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Man Wah Yeung
- Public Health Ontario, 480 University Avenue, Suite 300, Toronto, ON, M5G 1V2, Canada
| | - George Tomlinson
- Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College St, Toronto, ON, M5T 3M6, Canada.,Dalla Lana School of Public Health, University of Toronto, 155 College St, Toronto, ON, M5T 3M6, Canada.,University Health Network, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada
| | - Mark Loeb
- Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada
| | - Beate Sander
- Public Health Ontario, 480 University Avenue, Suite 300, Toronto, ON, M5G 1V2, Canada. .,Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College St, Toronto, ON, M5T 3M6, Canada. .,Institute for Clinical Evaluative Sciences, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. .,Toronto Health Economics and Technology Assessment (THETA) Collaborative, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.
| |
Collapse
|
|
47
|
Yeung MW, Shing E, Nelder M, Sander B. Epidemiologic and clinical parameters of West Nile virus infections in humans: a scoping review. BMC Infect Dis 2017; 17:609. [PMID: 28877682 PMCID: PMC5588625 DOI: 10.1186/s12879-017-2637-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 07/25/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Clinical syndromes associated with West Nile virus (WNV) infection range from fever to neuroinvasive disease. Understanding WNV epidemiology and disease history is important for guiding patient care and healthcare decision-making. The objective of this review was to characterize the existing body of peer-reviewed and surveillance literature on WNV syndromes and summarize epidemiologic and clinical parameters. METHODS We followed scoping review methodology described by the Joanna Briggs Institute. Terms related to WNV epidemiology, hospitalization, and surveillance were searched in four bibliographic databases (MEDLINE, EMBASE, Scopus, and CINAHL) for literature published from January 1999 to December 2015. RESULTS In total, 2334 non-duplicated titles and abstracts were screened; 92 primary studies were included in the review. Publications included one randomized controlled trial and 91 observational studies. Sample sizes ranged from under 25 patients (n = 19) to over 400 patients (n = 28). Eight studies were from Canada, seven from Israel, and the remaining (n = 77) from the United States. N = 17 studies were classified as outbreak case investigations following epidemics; n = 37 with results of regional/national surveillance and monitoring programs. Mean patient ages were > 40 years old; three studies (3%) focused on the pediatric population. Patients with encephalitis fared worse than patients with meningitis and fever, considering hospitalization, length of stay, discharge, recovery, and case-fatality. Several studies examined risk factors; however, age was the only risk factor for neuroinvasive disease/death consistently identified. Overall, patients with acute flaccid paralysis or encephalitis fared worse than patients with meningitis and West Nile fever in terms of hospitalization and mortality. Among the included studies, proportion hospitalized, length of stay, proportion discharged home and case-fatality ranged considerably. CONCLUSION Our review highlights the heterogeneity among reporting clinical WNV syndromes and epidemiologic parameters of WNV-related illness. Presently, there is potential for further synthesis of the risk factors of WNV-illness and mortality; undertaking further analysis through a systematic review and meta-analysis may benefit our understanding of risk factors for emerging mosquito-borne diseases. Future research on the burden of WNV can build on existing evidence summarized in this review, not only to support our understanding of endemic WNV, but also to strengthen research on emerging arboviruses with similar clinical manifestations.
Collapse
Affiliation(s)
- Man Wah Yeung
- Public Health Ontario, Toronto, Canada, Institute for Clinical Evaluative Sciences, Toronto, Canada, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - Emily Shing
- Public Health Ontario, Toronto, Canada, Institute for Clinical Evaluative Sciences, Toronto, Canada, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - Mark Nelder
- Public Health Ontario, Toronto, Canada, Institute for Clinical Evaluative Sciences, Toronto, Canada, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - Beate Sander
- Public Health Ontario, Toronto, Canada, Institute for Clinical Evaluative Sciences, Toronto, Canada, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| |
Collapse
|
|
48
|
Abstract
Although long recognized as a human pathogen, West Nile virus (WNV) emerged as a significant public health problem following its introduction and spread across North America. Subsequent years have seen a greater understanding of all aspects of this viral infection. The North American epidemic resulted in a further understanding of the virology, pathogenesis, clinical features, and epidemiology of WNV infection. Approximately 80% of human WNV infections are asymptomatic. Most symptomatic people experience an acute systemic febrile illness; less than 1% of infected people develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or anterior myelitis resulting in acute flaccid paralysis. Older age is associated with more severe illness and higher mortality; other risk factors for poor outcome have been challenging to identify. In addition to natural infection through mosquito bites, transfusion- and organ transplant-associated infections have occurred. Since there is no definitive treatment for WNV infection, protection from mosquito bites and other preventative measures are critical. WNV has reached an endemic pattern in North America, but the future epidemiologic pattern is uncertain.
Collapse
|
|
49
|
Abstract
Emerging zoonoses have had a serious impact on human and animal health in recent decades. More often than not, these disease outbreaks have taken public health by surprise because we have failed to shift the epidemiological curve to the far left and detect zoonoses in animal populations prior to spillover to people. Not only can animals serve as valuable sentinels for emerging zoonoses but also much can be gained by the study of the animals themselves.
Collapse
Affiliation(s)
- Tracey S McNamara
- Tracey S. McNamara is Professor of Pathology in the College of Veterinary Medicine at Western University of Health Sciences in Pomona, California
| |
Collapse
|
|
50
|
Burkett-Cadena ND, Gibson J, Lauth M, Stenn T, Acevedo C, Xue RD, McNelly J, Northey E, Hassan HK, Fulcher A, Bingham AM, van Olphen J, van Olphen A, Unnasch TR. Evaluation of the Honey-Card Technique for Detection of Transmission of Arboviruses in Florida and Comparison With Sentinel Chicken Seroconversion. JOURNAL OF MEDICAL ENTOMOLOGY 2016; 53:1449-1457. [PMID: 27330092 DOI: 10.1093/jme/tjw106] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/26/2016] [Indexed: 06/06/2023]
Abstract
Zoonotic mosquito-borne viruses, such as the West Nile virus (WNV) and eastern equine encephalitis virus (EEEV), are major public health threats in the United States. Early detection of virus transmission and targeted vector management are critical to protect humans against these pathogens. Sentinel chickens and pool screening of mosquitoes, the most widely used methods of arbovirus early detection, have technical time-lags that compromise their early-detection value. The exploitation of sugar-feeding by trapped mosquitoes for arbovirus surveillance may represent a viable alternative to other methods. Here we compared effectiveness of sugar-impregnated nucleic-acid preserving substrates (SIPS) and sentinel chicken program for detecting WNV, EEEV, and St. Louis encephalitis virus in gravid traps, CO2-baited light traps, and resting traps at 10 locations in two Florida counties. In St. Johns County, comparable numbers of EEEV detections were made by SIPS traps (18) and sentinel chickens (22), but fewer WNV detections were made using SIPS (1) than sentinel chickens (13). In Volusia County, seven arbovirus detections were made via the sentinel chicken program (one EEEV and six WNV), whereas only one arbovirus detection (WNV) was made using SIPS. CO2-baited light traps captured >90% of total mosquitoes, yet yielded <30% of arbovirus detections. Resting traps and gravid traps captured a fraction of total mosquitoes, yet yielded roughly equivalent numbers of arbovirus detections, as did light traps. Challenges to successful deployment of SIPS include optimization of traps for collecting all vector species, increasing sugar-feeding rates of trapped vectors, and developing tractable methods for arbovirus detection.
Collapse
Affiliation(s)
- Nathan D Burkett-Cadena
- University of Florida IFAS, Florida Medical Entomology Laboratory, 200 9th St. SE, Vero Beach, FL 32962 (; ; )
| | - Jennifer Gibson
- Anastasia Mosquito Control District, 500 Old Beach Road, St. Augustine, FL 32080 (; ; )
| | - Miranda Lauth
- Volusia County Mosquito Control, 801 South St, New Smyrna Beach, FL 32168 (; ; )
| | - Tanise Stenn
- University of Florida IFAS, Florida Medical Entomology Laboratory, 200 9th St. SE, Vero Beach, FL 32962 (; ; )
| | - Carolina Acevedo
- University of Florida IFAS, Florida Medical Entomology Laboratory, 200 9th St. SE, Vero Beach, FL 32962 (; ; )
| | - Rui-de Xue
- Anastasia Mosquito Control District, 500 Old Beach Road, St. Augustine, FL 32080 (; ; )
| | - James McNelly
- Volusia County Mosquito Control, 801 South St, New Smyrna Beach, FL 32168 (; ; )
| | - Edward Northey
- Volusia County Mosquito Control, 801 South St, New Smyrna Beach, FL 32168 (; ; )
| | - Hassan K Hassan
- Global Health Infectious Disease Program, University of South Florida, 3720 Spectrum Blvd., Tampa, FL 33612 (; ; ; ; )
| | - Ali Fulcher
- Anastasia Mosquito Control District, 500 Old Beach Road, St. Augustine, FL 32080 (; ; )
| | - Andrea M Bingham
- Global Health Infectious Disease Program, University of South Florida, 3720 Spectrum Blvd., Tampa, FL 33612 (; ; ; ; )
- Present Address: Florida Department of Health, Division of Disease Control and Health Protection, Bureau of Epidemiology, 4052 Bald Cypress Way, Bin # A12, Tallahassee, Florida 32399-1710, and
| | - Jose van Olphen
- Global Health Infectious Disease Program, University of South Florida, 3720 Spectrum Blvd., Tampa, FL 33612 (; ; ; ; )
| | - Alberto van Olphen
- Global Health Infectious Disease Program, University of South Florida, 3720 Spectrum Blvd., Tampa, FL 33612 (; ; ; ; )
- Present Address: Clemson University, Clemson Veterinary Diagnostic Center, PO Box 102406, Columbia, South Carolina 29224-2406
| | - Thomas R Unnasch
- Global Health Infectious Disease Program, University of South Florida, 3720 Spectrum Blvd., Tampa, FL 33612 (; ; ; ; )
| |
Collapse
|