Encephalitis In China Research Articles

TaqMan qPCR and IgM Detection in Samples of Patients with Tick-Borne Encephalitis Virus Infection in Northeast China.

Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study. This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics. Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients. Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.

Metagenomic sequencing reveals viral diversity of mosquitoes from Shandong Province, China.

Mosquitoes are known as the source of various pathogens for humans and animals. Culex tritaeniorhynchus, Armigeres subalbatus, and Anopheles sinensis have been found to transmit the Getah virus, which has recently caused increasing infections in China. Cx. tritaeniorhynchus and Culex pipiens are the main vectors of Japanese encephalitis virus and have caused epidemics of Japanese encephalitis in China in past decades. These mosquitoes are widely present in Shandong Province, China, leading to a great threat to public health and the breeding industry. This study provided a comprehensive insight into the viromes of several common mosquito species in Shandong Province, China. The metagenomic sequencing data revealed the risks of multiple pathogenic mosquito-borne viruses, including Japanese encephalitis virus, Getah virus, and Kadipiro virus, which are of great importance for preventing emerging viral epidemics.

Effects of adjunctive Chinese patent medicine on outcome of viral encephalitis in children: A multicenter retrospective study in China

BackgroundSome patients with viral encephalitis in China seek treatment with Chinese patent medicine (CPM) to improve their symptoms, but few studies have focused on the impact of CPM on the prognosis of viral encephalitis (VE). The aim of this multicenter retrospective study was to assess the benefit of adjunctive CPM therapy on the outcome of children with VE in China. MethodsThis study retrospectively included 834 children with viral encephalitis who were hospitalized at five medical institutions from 2018 to 2021. Univariate and multivariate logistic regression was used to assess the effect of CPM on sequelae in patients with VE. 1:1 propensity score matching was used to exclude the effect of confounding factors. Forest plots were used to observe the effect of CPM on the prognosis of VE in different subgroups. ResultsThere were fewer patients with sequelae in the group of patients using CPM regardless of whether they were matched or not. The results of multivariate logistic regression analysis showed that the use of CPM was an independent protective factor for the development of sequelae in VE patients (OR = 0.063, 95 % CI: 0.011–0.350, p = 0.002). Subgroup analyses showed that CPM was a protective factor for the development of sequelae regardless of the presence or absence of coma and comorbidities. In addition, we evaluated other outcome indicators and found shorter duration of illness, fever and headache in children with EV in the CPM group. ConclusionAdjunctive CPM therapy may significantly reduce sequelae in children with VE, as well as effectively alleviate patients' clinical symptoms. However, more prospective studies and clinical trials are needed to further evaluate its efficacy and safety.

Pathogenic free-living amoebic encephalitis from 48 cases in China: A systematic review.

Free-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China. We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions. After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated. This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.

Coexistence of multiple anti-neuronal antibodies in autoimmune encephalitis in China: A multi-center study.

BackgroundGiven that the combination of multiple antibodies in autoimmune encephalitis (AE) is rare and its clinical significance is unclear, this study aimed to investigate the clinical characteristics and significance of overlapping multiple anti-neuronal antibodies in patients with AE.MethodsWe conducted a retrospective analysis of the clinical characteristics, treatment, and prognostic details of 22 patients with multiple coexisting antibodies from multiple clinical centers in China.ResultsAmong the 276 patients who were AE antibody-positive, 22 (7.97%) had two or more antibodies. Among the 22 patients with coexisting AE-related antibodies, 14 patients (63.63%) were combined of cell surface and intracellular antibody, and the remaining 8 patients (36.36%) were detected to be cell surface antibody positive only. The main symptoms of the 22 patients in this cohort included fever, seizures, memory impairment, cognitive decline, and sleep disorders. Five (22.73%) patients had tumors, among whom four had small-cell lung cancers, and one had mediastinal tumors. A total of 20 patients were treated with steroids and intravenous immunoglobulin, and 18 showed varying degrees of symptomatic improvement after first-line immunotherapy. Three patients died of tumor progression or chemotherapy complications.ConclusionThe coexistence of multiple anti-neuronal antibodies in patients with AE may cause a superimposition and diversification of clinical manifestations. Combined paraneoplastic antibody positivity may be suggestive of an underlying malignancy.

Clinical characteristics and prognosis of anti-γ-aminobutyric acid-B receptor encephalitis: A single-center, longitudinal study in China.

ObjectiveAnti-γ-aminobutyric acid-B receptor (GABABR) encephalitis is a rare type of autoimmune encephalitis. There are only a few, small, published studies regarding prognosis, so prediction of prognosis is of limited accuracy. We identified 37 cases of anti-GABABR encephalitis in China. Here, we present these patients' clinical characteristics and long-term outcomes.MethodsWe collected and retrospectively analyzed the clinical data of 37 patients with anti-GABABR encephalitis from Beijing Fengtai You'anmen Hospital.ResultsThe study cohort comprised 37 patients of anti-GABABR encephalitis of median age 61 years (range: 11–77), 28 of whom were male. The main clinical manifestations were epilepsy (91.9%, 34/37), psychiatric disorders (94.6%, 35/37) and cognitive impairment (97.3%, 36/37). Tumors were identified in 18 (48.6%) patients. First-line immunotherapy was administered to 34 patients, 31 of whom (90.6%) responded favorably. During a median follow-up of 18 months (range: 1–72 months), 21 patients had good outcomes [Modified Ranking Scale (mRS ≤2)], 16 (43.2%) died (mRS 6), and 7 (18.9%) relapsed. Age (P = 0.005), disturbance of consciousness (P = 0.018), admission to the Neurology Intensive Care Unit (P = 0.003), mechanical ventilation (P = 0.009), more numerous clinical manifestations (P = 0.008), comorbid malignancy (P = 0.008), multiple anti-neuronal antibodies (P = 0.029), and hyponatremia (P = 0.023) differed significantly between patients with good outcomes (mRS 0–2) and those with poor outcomes (mRS 3–6).ConclusionMen aged 50–70 years accounted for most of the patients with anti-GABABR encephalitis in our case series. The main clinical manifestations were epilepsy and neuropsychiatric dysfunction. The participants often had concomitant lung cancer, particularly small-cell lung cancer. Patients with lung tumors and/or serious manifestations usually had a poor prognosis with high mortality. Early identification and treatment of tumors improved the poor prognosis to some extent.

Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study

SummaryBackgroundAcute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China.MethodsNation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods.FindingsBetween 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18−59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5−17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18−59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3−6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased.InterpretationThe current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy.FundingChina Mega-Project on Infectious Disease Prevention and the National Natural Science Funds

The prognosis of late-onset anti-N-methyl-D-aspartate receptor encephalitis in China.

Early-onset anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) differs from late-onset anti-NMDARE regarding clinical characteristics. Until recently, research focusing on prognosis of elder adults has been scarce and showed inconsistent results. This study aims to evaluate the prognosis of late-onset anti-NMDARE in China. One hundred and twelve adults diagnosed as anti-NMDARE in four hospitals in China were reviewed retrospectively. Outcome data were assessed using modified Rankin Scale (mRS) score in short term (3months after discharge) and long term (≥12months after discharge). The relapse rate was also computed. Multivariable logistic regression was used to evaluate whether there are substantial differences in functional outcomes and recurrence rate across two groups. Of the 112 patients with anti-NMDARE, 81 (72.3%) were early-onset disease and 31 (27.7%) were late-onset disease. Of these, all had short-term follow-up and 70 completed long-term follow-up. Late-onset anti-NMDARE group showed better short-term (OR 2.70, 95% CI 1.09-6.71) and long-term prognoses (OR 10.25, 95% CI 1.90-55.15). Recurrence rates were statistically different between the groups (OR 4.25, 95% CI 1.22-14.75). The prognosis for anti-NMDARE in China was poorer for older adults relative to younger adults. The relapse rates were higher in late-onset group compared to early-onset group.

The changing spectrum of antibody-mediated encephalitis in China

In the past 5 years, the positivity rate of autoimmune encephalitis antibody panels has significantly decreased in patients with clinically suspected encephalitis in an encephalitis center in China. Furthermore, the spectrum of patients with autoantibodies related to autoimmune encephalitis has changed significantly, exhibiting a decreased percentage of patients with anti-N-methyl-d-aspartate receptor antibodies and an increased percentage of patients with infrequently observed autoantibodies. Meanwhile, a small but non-negligible proportion of patients with autoantibodies against cell surface and synaptic proteins exhibited positivity for more than one autoantibody.

Genetic structure of Culex tritaeniorhynchus (Diptera: Culicidae) based on COI DNA barcodes

Culex tritaeniorhynchus Gile is a major vector of Japanese encephalitis in China. The population genetics study is crucial as it helps understanding the epidemiological aspects of mosquito-brone diseases and improving vector control measures. Here, the genetic population structure of C. tritaeniorhynchus in the mainland China were estimated using the cytochrome c oxidase subunit 1 (COI) DNA barcodes region. 485 individuals of C. tritaeniorhynchus were collected from 38 sampling sites in 21 geographic populations in the mainland China. In total, 485 sequences were used to explore the population structure and genetic diversity. The results showed that the populations of C. tritaeniorhynchus had high haplotype diversity (Hd = 0.98, with 303 haplotypes), low nucleotide diversity (p = 0.02245) and high gene flow (Nm = 47.11) with two maternal lineages and four groups. An AMOVA indicated that 98.8% of the total variation originated from variation within populations. In addition, the population genetic structure exhibited by C. tritaeniorhynchus filling the vacant of the genetic structure in the mainland China. Human activities may also assist mosquito movement and migration. Gene flow among the populations of C. tritaeniorhynchus can facilitate the spread of insecticide resistance genes over geographical areas, and it will be a challenging for controlling the populations.

Neuronal Surface Antibody-Medicated Autoimmune Encephalitis (Limbic Encephalitis) in China: A Multiple-Center, Retrospective Study.

Objective: The epidemiological characteristics of patients with antibody-medicated autoimmune encephalitis in China remain unclear, and a large-scale epidemiological survey is necessary.Methods: A multiple-center retrospective study was performed. We collected 1,047 patients with suspected autoimmune encephalitis and ultimately enrolled 778 defined patients across centers in China. All patients were positive for serum [or cerebrospinal fluid (CSF)] antibodies. Demographic information and clinical data from January 2014 to January 2019 from 22 centers in China were reviewed.Results: A total of 778 patients with autoimmune encephalitis were enrolled in the study. In general, the ratio of males to females was ~1.2:1. The main subtypes of autoimmune encephalitis were NMDAR-AE (61.35%), LGI-1-AE (20.61%), and GABAbR-AE (12.40%). According to the characteristics of age of onset, the incidence of autoimmune encephalitis showed a “double peak” distribution entailing a 20-year-old age group and a 60-year-old age group. We next analyzed the proportion of patients with tumors in this cohort. More specifically, there were 34 patients with tumors and 85 with tumor marker positivity. Relapse occurred in 81 patients within at least 1 year's follow up study: 52 with NMDAR-AE (18.2%); 19 with LGI-1-AE (16.8%); 5 with GABAbR-AE (9%); and 3 with CASPR2-AE.Interpretation: Due to the vast differences in demographic features, the incidence of cancer and the genetic characteristics between the populations in China and Western countries, the demographics, sex distribution, concomitant tumor rate, clinical features, and relapse characteristics associated with autoimmune encephalitis in China shows a similar profile with Western countries with some minor differences.

A potential new recombinant echovirus 18 strain detected in a 4-year-old child with encephalitis in China in 2019.

The species Enterovirus B includes diverse serotypes that can cause a wide spectrum of human diseases, such as aseptic encephalitis, myocarditis, and paralysis. In this study, a 4-year-old child was diagnosed with viral encephalitis, but the causative agent could not be identified using routine immunological tests. Using metagenomic RNA sequencing, a novel strain of enterovirus B, strain PC06, was identified, and its genome sequence was determined by RT-PCR and Sanger sequencing. The viral genome sequence was most similar to that of echovirus E18 strain E18-HeB15-54498/HeB/CHN/2015 (GenBank accession MG720261), with 87.73% nucleotide sequence identity, while the viral proteins shared 96.98% amino acid sequence identity with those of E18 strain Jena/AN1365/10 (GenBank accession no. KX139452). Phylogenetic analysis based on the VP1 and 3D genes revealed discrepant placement of PC06 in the two trees. In the 3D tree, PC06 formed a separate branch together with other recombinant E18 strains. Further recombination tests revealed that PC06 had possibly undergone recombination at a site between the structural and non-structural regions during its evolutionary history. Based on the analysis of VP1 phylogeny and using online genotyping tools, this potential recombinant is tentatively considered a strain of echovirus 18. This information might contribute to the diagnosis and prevention of related diseases.

Clinical features, treatments, and outcomes of patients with anti-N-methyl-D-aspartate encephalitis-a single-center, retrospective analysis in China.

Objective: To describe the clinical features, laboratory data, treatment, and outcomes of anti-N-methyl-D-aspartate (NMDAR) encephalitis in Chinese patients. Methods: This retrospective study included hospitalized patients definitively diagnosed with anti-NMDAR encephalitis and positive for anti-NMDAR antibodies in the cerebrospinal fluid (CSF) in Shenzhen People's hospital, between November 2015 and February 2020. The clinical manifestation, laboratory data, treatments and outcomes were collected retrospectively. Patients were followed up for more than 1 year. Results: The study included 31 patients (15 men, 48.4%) with a median age of 31 years (interquartile range 21-48). The most common clinical presentations were psychosis (n = 23, 74.2%), seizures (n = 20, 64.5%), and memory impairment (n = 20, 64.5%). Total magnetic resonance imaging abnormalities were found in 11 patients (35.5%), with the medial temporal and frontal lobes as the most commonly involved. Abnormal electroencephalogram was observed in 16 patients (51.6%). Five out of 31 patients (19.5%) were diagnosed as neoplasm, including five females with ovarian teratoma and one male with a central nervous system tumor. Multiple immune antibodies, including anti-SSA antibody in four patients (15.4%), anti-Ro52 antibody in four (15.4%), antinuclear antibody (ANT) in four (15.4%), anti-thyroglobulin antibodies (TGAb) in five (17.2%), and thyroid peroxidase antibodies (TPOAb) in three (10.3%) were present. All patients received first-line immunization therapy (intravenous immunoglobulin, glucocorticoids, or plasmapheresis alone or combined), and only two patients (7.3%) received second-line immunization therapy (rituximab). Mechanical ventilation was more necessary in women (37.5%) than in men (6.7%) (p = 0.04), and 29 (93.5%) had favorable clinical outcomes. At more than 12 months of follow-up, the median modified Rankin Scale score decreased from 4 to 0. Conclusions: Patients with anti-NMDAR encephalitis in China had high rates of psychosis and seizures, with low rates of underlying neoplasms. A higher proportion of female patients required mechanical ventilation. Complications with other positive autoimmune antibodies were a common clinical symptoms of anti-NMDAR encephalitis. Majority of the patients obtained satisfactory outcomes in combination with early first-line and long-term immunization therapy.

Epidemic Changes and Spatio-Temporal Analysis of Japanese Encephalitis in Shaanxi Province, China, 2005-2018.

Japanese encephalitis (JE) is a mosquito-borne viral disease, which is the most serious viral encephalitis in China and other countries of the Asia-Pacific region. Since 2005, the epidemic patterns of JE have changed dramatically in China because of the vaccination of children younger than 15 years old, and JE is expanding geographically along with global warming. This retrospective epidemiological study analyzed dynamic environmental factors and the spatio-temporal distribution of human cases of JE in Shaanxi Province—one of the most severely affected areas of China—from 2005 to 2018. The results demonstrated that the high-risk population changed rapidly as the annual rate of JE cases increased by more than 40% in the age group >60 years during the study period, and endemic areas expanded northward in Shaanxi. Hotspot analysis detected four hotspots accounting for 52.38% the total cases, and the panel negative binomial regression model revealed that the spatio-temporal distribution of JE was significantly affected by temperature, relative humidity, wind velocity, El Niño-Southern Oscillation, coniferous forest coverage, and urban areas. These findings can provide useful information for improving current strategies and measures to reduce disease incidence.

Keeping pace with the world: improving the clinical practice of anti-NMDAR encephalitis in China.

Keeping pace with the world: improving the clinical practice of anti-NMDAR encephalitis in China.

Clinical Characteristic Analysis of Seven Children With Bickerstaff Brainstem Encephalitis in China.

Objective: To summarize the clinical, electrophysiological, neuroimaging, and immunological characteristics of seven cases of Bickerstaff brainstem encephalitis (BBE) in China and to determine whether certain clinical features suggestive of BBE can facilitate diagnosis and treatment.Patients and Methods: The clinical data of seven BBE patients treated at the Children's Hospital of Fudan University between 2016 and 2019 were retrospectively analyzed. The clinical and laboratory characteristics of the BBE patients were studied.Results: The seven patients in this study included four females and three males, and the median age at diagnosis was 5.3 years (interquartile range: 3.0–7.1 years). All seven patients had an acute onset with a preinfection history. Seven cases of acute extraocular paralysis, ataxia, and an impaired level of consciousness, two cases of tendon hyperreflexia, one case of positive pathology, and five cases of cranial nerve involvement (the facial nerve and oculomotor nerve) were noted. Cerebrospinal fluid (CSF) examination of five patients showed albuminocytologic dissociation. Electromyography (EMG) was used to examine seven patients; the results were normal in four patients, showed axonal involvement in two patients, and showed demyelination in one patient. The head magnetic resonance imaging (MRI) results of all seven patients were normal. Electroencephalogram (EEG) background activity in the five monitored patients was slowed down. Seven patients underwent serum antibody testing, three of whom were positive for anti-GQ1b antibody, while one was positive for anti-GM1 antibody. Three patients received glucocorticoid combined with intravenous immunoglobulin (IVIG) therapy, and four received only IVIG therapy. One patient required a nasal catheter for oxygen during the disease course, and left upper limb muscle dysfunction (grade III muscle strength of the left upper limb) was observed during the 6-month follow-up. The other six patients had a good prognosis and no dysfunction.Conclusion: Our study identified clinical, imaging, and treatment characteristics that may have prognostic value for pediatric BBE. The positive rate of head MRI was low, the positive rate of serum anti-GQ1b ganglioside antibody was low, and the therapeutic effect of IVIG therapy was good.

Psychiatric Symptoms of Patients With Anti-NMDA Receptor Encephalitis.

Objective: We conducted this study to analyze the clinical characteristics of the psychiatric symptoms of patients with anti-NMDAR encephalitis.Methods: A retrospective study of anti-NMDAR encephalitis in China was performed. The clinical characteristics of the psychiatric symptoms, the relationship between the antibodies titers and clinical characteristics of patients with anti-NMDAR encephalitis were determined.Results: A total of 108 patients with a definitive diagnosis of anti-NMDAR encephalitis were included in this study. 103 patients (95%) developed one or several psychiatric symptoms. The comparison of the high titer group and the low titer group showed that more patients presented psychiatric symptoms as the initial symptom in the high titer group (P = 0.020), the prevalence of the symptoms such as depressive, catatonic, and central hypoventilation were also higher in the high titer group than the low titer group (P = 0.033, 0.031 and 0.006, respectively). Meanwhile, more patients received a combination treatment of IVIg and corticosteroids in the high titer group than the low titer group and patients in high titer group were prescript with anti-psychiatric drugs more often than the patients in low titer group (P = 0.026 and 0.003, respectively).Conclusions: Psychiatric symptoms are the most common clinical characteristics of patients with anti-NMDAR encephalitis. Patients with higher antibodies titers more often presented with psychiatric symptoms as the initial symptom, and showed a more severe clinical feature. Screening for the anti-NMDAR antibodies is essentially important in patients who present psychiatric symptoms with or without other neurological symptoms.

Clinical Features, Treatment, and Outcomes Among Chinese Children With Anti-methyl-D-aspartate Receptor (Anti-NMDAR) Encephalitis.

Objective: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common form of autoimmune encephalitis in pediatric patients. In this study, we aimed to investigate the clinical features and long-term outcomes of pediatric patients with anti-NMDAR encephalitis in China.Methods: We conducted a retrospective study of children (age range: 0–18 years) with anti-NMDAR encephalitis treated at Children's Hospital of Fudan University between July 2015 and November 2018. Demographic characteristics, clinical features, treatment, and outcomes were reviewed.Results: Thirty-four patients with anti-NMDAR encephalitis were enrolled (age range: 5 months to 14 years; median age: 7 years; female: 18). The median follow- up duration was 20 months (range: 6–39 months). Eighteen (52.9%) patients initially presented with seizures and 10 (29.4%) with abnormal (psychiatric) behaviors or cognitive dysfunction. Thirty (88.2%) patients exhibited more than two symptoms during the disease course. No neoplasms were detected. Twelve (35.2%) patients had abnormal cerebrospinal fluid (CSF) findings, including leukocytosis, and increased protein concentration. Eighteen (52.9%) patients exhibited normal brain MRI findings. Electroencephalography revealed abnormal background activity in 27 (79.4%) patients, and epileptiform discharges in 16 (47.0%) patients prior to immunotherapy. All patients received first-line immunotherapy, with 30 (88.2%) and four (11.8%) patients achieving good (Modified Rankin Scale [mRS] score of 0–2) and poor outcomes (mRS score of 3–5), respectively. Initial mRS scores differed significantly between the good and poor outcome groups. Fourteen out of 18 patients (77.7%) with seizures accepted anti-epileptic drug (AED) administration, and seizure freedom was achieved in 12 out of 14 (85.7%) patients at the last follow-up. Ten of these 12 (83.3%) patients withdrew from AED treatment within 1 year.Conclusions: Most patients achieved seizure freedom, so long-term use of AEDs may not be necessary for pediatric patients with anti-NMDAR encephalitis. Among our patients, 83.3% were sensitive to first-line immunotherapy and achieved good outcomes. Higher mRS scores before immunotherapy predicted poor outcomes, highlighting the need for a comprehensive assessment of patients with anti-NMDAR encephalitis.

The progress and challenge of Japanese encephalitis control and prevention in China

Japanese encephalitis (JE) is the important viral encephalitis in China. In the 1940s, JE was confirmed to be epidemic in China. In 1971, the annual incidence rate was 20.92/100 000. Since 2008, JE vaccine was included in the national Expanded Program of Immunization (EPI). In 2013, the incidence of Japanese encephalitis decreased to 0.16/100 000. JE virus is divided into five genotypes, and genotype 1, 3 and 5 JE virus was isolated in China. Genotype 1 JE virus was the mainly genotype currently circulated in China. In recent years, the characteristics of the population of JE have been changed to adult, especially in the northern provinces of China. JE prevention and control faces new challenges.

Epidemiology of Japanese Encephalitis in China (2004–2015)

We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968–1987], the SA 14-14-2 live-attenuated vaccine strategy [1988–2007], and the Expanded Program on Immunization [EPI, 2008–2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels.The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis.After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001).Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.