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Jornal de Pediatria 2020To review the diagnostic criteria for encephalitis and encephalopathy of presumed infectious etiology, as well as the diagnostic workup for viral encephalitis and its... (Review)
Review
OBJECTIVES
To review the diagnostic criteria for encephalitis and encephalopathy of presumed infectious etiology, as well as the diagnostic workup for viral encephalitis and its treatment approaches. The authors also intended to summarize relevant information on specific viruses frequently found in Brazil.
SOURCE OF DATA
Literature search on Pubmed/MEDLINE using the following keywords: "viral", "encephalitis", "child", or "adolescents", filtering for articles on humans and in English.
SUMMARY OF DATA
Viral encephalitis is the most common cause of encephalitis and is responsible for high rates of morbidity, permanent neurologic sequelae, and according to the virus, may have high mortality rates. The most common etiologies are herpesviruses 1 and 2 (HSV-1 and HSV-2), non-polio enterovirus, and arboviruses (in Brazil, dengue, Zika, and chikungunya). Other relevant etiologies are seasonal influenza, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and the re-emergent measles.
CONCLUSION
Clinical data, laboratory results, and neuroimaging findings support the diagnosis of encephalitis and the specific viral etiology. To increase the likelihood of etiologic confirmation, it is important to know the best approach to collecting samples and to choose the best identification technique for each virus. The differential diagnosis of viral encephalitis includes other infections and immune-mediated inflammatory central nervous system disorders.
Topics: Adolescent; Brazil; Child; Cytomegalovirus; Encephalitis, Viral; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Zika Virus; Zika Virus Infection
PubMed: 31513761
DOI: 10.1016/j.jped.2019.07.006 -
Annals of Neurology Jan 2018To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis. (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.
METHODS
We performed a population-based comparative study of the incidence and prevalence of autoimmune and infectious encephalitis in Olmsted County, Minnesota. Autoimmune encephalitis diagnosis and subgroups were defined by 2016 diagnostic criteria, and infectious encephalitis diagnosis required a confirmed infectious pathogen. Age- and sex-adjusted prevalence and incidence rates were calculated. Patients with encephalitis of uncertain etiology were excluded.
RESULTS
The prevalence of autoimmune encephalitis on January 1, 2014 of 13.7/100,000 was not significantly different from that of all infectious encephalitides (11.6/100,000; p = 0.63) or the viral subcategory (8.3/100,000; p = 0.17). The incidence rates (1995-2015) of autoimmune and infectious encephalitis were 0.8/100,000 and 1.0/100,000 person-years, respectively (p = 0.58). The number of relapses or recurrent hospitalizations was higher for autoimmune than infectious encephalitis (p = 0.03). The incidence of autoimmune encephalitis increased over time from 0.4/100,000 person-years (1995-2005) to 1.2/100,000 person-years (2006-2015; p = 0.02), attributable to increased detection of autoantibody-positive cases. The incidence (2.8 vs 0.7/100,000 person-years, p = 0.01) and prevalence (38.3 vs 13.7/100,000, p = 0.04) of autoimmune encephalitis was higher among African Americans than Caucasians. The prevalence of specific neural autoantibodies was as follows: myelin oligodendrocyte glycoprotein, 1.9/100,000; glutamic acid decarboxylase 65, 1.9/100,000; unclassified neural autoantibody, 1.4/100,000; leucine-rich glioma-inactivated protein 1, 0.7/100,000; collapsin response-mediator protein 5, 0.7/100,000; N-methyl-D-aspartate receptor, 0.6/100,000; antineuronal nuclear antibody type 2, 0.6/100,000; and glial fibrillary acidic protein α, 0.6/100,000.
INTERPRETATION
This study shows that the prevalence and incidence of autoimmune encephalitis are comparable to infectious encephalitis, and its detection is increasing over time. Ann Neurol 2018;83:166-177.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Black People; Child; Child, Preschool; Encephalitis; Female; Hashimoto Disease; Hospitalization; Humans; Incidence; Infant; Infant, Newborn; Infectious Encephalitis; Male; Middle Aged; Prevalence; Recurrence; United States; White People; Young Adult
PubMed: 29293273
DOI: 10.1002/ana.25131 -
Human Vaccines & Immunotherapeutics 2014Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV... (Review)
Review
Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development.
Topics: Animals; Asia; Cell Line; Drug Discovery; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Technology, Pharmaceutical; Vaccination
PubMed: 24161909
DOI: 10.4161/hv.26902 -
JAMA Jul 2013Since its introduction in North America in 1999, West Nile virus has produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in the United States. (Review)
Review
IMPORTANCE
Since its introduction in North America in 1999, West Nile virus has produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in the United States.
OBJECTIVE
To review the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus, with an emphasis on North America.
EVIDENCE REVIEW
PubMed electronic database was searched through February 5, 2013. United States national surveillance data were gathered from the Centers for Disease Control and Prevention.
FINDINGS
West Nile virus is now endemic throughout the contiguous United States, with 16,196 human neuroinvasive disease cases and 1549 deaths reported since 1999. More than 780,000 illnesses have likely occurred. To date, incidence is highest in the Midwest from mid-July to early September. West Nile fever develops in approximately 25% of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1% but carries a fatality rate of approximately 10%. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs. Diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. Treatment is supportive; no licensed human vaccine exists. Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible.
CONCLUSIONS AND RELEVANCE
In North America, West Nile virus has and will remain a formidable clinical and public health problem for years to come.
Topics: Animals; Birds; Culicidae; Ecology; Humans; Mosquito Control; United States; West Nile Fever; West Nile virus
PubMed: 23860989
DOI: 10.1001/jama.2013.8042 -
Clinical Microbiology Reviews Mar 2020Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral... (Review)
Review
Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.
Topics: Acyclovir; Adrenal Cortex Hormones; Animals; Antiviral Agents; Drug Therapy; Encephalitis, Herpes Simplex; Genetic Predisposition to Disease; Humans; Immunity; Immunomodulation; Risk Factors; Simplexvirus; Treatment Outcome
PubMed: 32051176
DOI: 10.1128/CMR.00105-19 -
Rhode Island Medical Journal (2013) Aug 2020Travelers to 24 endemic countries in Asia may be at risk for Japanese encephalitis. The ACIP has recently expanded guidelines on the use of Ixiaro, the inactivated... (Review)
Review
Travelers to 24 endemic countries in Asia may be at risk for Japanese encephalitis. The ACIP has recently expanded guidelines on the use of Ixiaro, the inactivated Japanese encephalitis vaccine. This article reviews the disease burden of Japanese encephalitis and the role of a travel clinic in guiding travelers to Asia regarding decision-making about the use of this highly protective vaccine.
Topics: Adolescent; Adult; Asia; Child; Child, Preschool; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Infant; Japanese Encephalitis Vaccines; Risk; Seasons; Travel
PubMed: 32752568
DOI: No ID Found -
Infectious Disease Clinics of North... Sep 2022Powassan virus is an increasingly recognized cause of severe encephalitis that is transmitted by Ixodes ticks. Given the nonspecific clinical, laboratory, and imaging... (Review)
Review
Powassan virus is an increasingly recognized cause of severe encephalitis that is transmitted by Ixodes ticks. Given the nonspecific clinical, laboratory, and imaging features of Powassan virus disease, providers should consider it in patients with compatible exposures and request appropriate testing.
Topics: Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Humans
PubMed: 36116842
DOI: 10.1016/j.idc.2022.03.003 -
Nature Nov 2023Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells...
Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6). Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4 T cells. Using single-cell sequencing, we identify a rare population of HHV-6 'super-expressors' (about 1 in 300-10,000 cells) that possess high viral transcriptional activity, among research-grade allogeneic chimeric antigen receptor (CAR) T cells. By analysing single-cell sequencing data from patients receiving cell therapy products that are approved by the US Food and Drug Administration or are in clinical studies, we identify the presence of HHV-6-super-expressor CAR T cells in patients in vivo. Together, the findings of our study demonstrate the utility of comprehensive genomics analyses in implicating cell therapy products as a potential source contributing to the lytic HHV-6 infection that has been reported in clinical trials and may influence the design and production of autologous and allogeneic cell therapies.
Topics: Humans; CD4-Positive T-Lymphocytes; Clinical Trials as Topic; Gene Expression Regulation, Viral; Genomics; Herpesvirus 6, Human; Immunotherapy, Adoptive; Infectious Encephalitis; Receptors, Chimeric Antigen; Roseolovirus Infections; Single-Cell Gene Expression Analysis; Viral Load; Virus Activation; Virus Latency
PubMed: 37938768
DOI: 10.1038/s41586-023-06704-2 -
Clinical Microbiology and Infection :... Sep 2017Infectious encephalitis is a rare but severe medical condition resulting from direct invasion of the brain by viruses, bacteria, fungi or parasites, or indirect... (Review)
Review
Infectious encephalitis is a rare but severe medical condition resulting from direct invasion of the brain by viruses, bacteria, fungi or parasites, or indirect post-infectious immune or inflammatory disorders when the infectious agent does not cross the blood-brain barrier. Infectious encephalitis cases represent an interesting and accurate sentinel to follow up on trends in infectious diseases or to detect emerging infections. Using Pubmed and Embase, we searched the most relevant publications over the last years. We present here an update on the important findings and new data recently published about infectious encephalitis.
Topics: Central Nervous System Protozoal Infections; Humans; Infectious Encephalitis; Molecular Diagnostic Techniques; Naegleria fowleri; Practice Guidelines as Topic; RNA Viruses
PubMed: 28501667
DOI: 10.1016/j.cmi.2017.05.002 -
MBio Aug 2023Survivors of Powassan encephalitis often have persistent neurological disease. A new mouse model replicates some elements of the human disease and demonstrates the...
Survivors of Powassan encephalitis often have persistent neurological disease. A new mouse model replicates some elements of the human disease and demonstrates the presence of viral RNA in the brain as well as myelitis more than 2 mo after the acute infection. The related tick-borne encephalitis and West Nile Neuroinvasive Disease (WNND) also have common neurological sequelae, and models for these better-studied diseases provide evidence for prolonged virus, RNA, and inflammation in some cases, in addition to damage from the acute encephalitic disease. A better understanding of the biological basis for persistent signs and symptoms after Powassan encephalitis, currently a rare disease, could benefit from further studies of the more prevalent flaviviral encephalitides.
Topics: Animals; Mice; Humans; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Mice, Inbred C57BL; Flavivirus Infections; Nervous System Diseases
PubMed: 37338444
DOI: 10.1128/mbio.00712-23