The epidemiology of acute encephalitis.

Encephalitis means inflammation of the brain matter. Despite being a rare condition, encephalitis is of public health importance worldwide because it has high morbidity and mortality. Yet, many details about its epidemiology have yet to be elucidated. This review attempts to summarise what is known about the epidemiology of the infective causes of encephalitis and is based on a literature search of the Medline archives. Infection is the most common cause identified, with viruses being the most important known aetiological agents. Incidence varies between studies but is generally between 3.5 and 7.4 per 100,000 patient-years. Encephalitis affects peoples of all ages; however, incidence is higher in the paediatric population. Although both sexes are affected, most studies have shown a slight predominance in males. Encephalitis occurs worldwide; some aetiologies have a global distribution (herpesviruses) while others are geographically restricted (arboviruses). Although definite epidemiological trends are evident, it is difficult to make generalisations as few population-based studies exist, most cases are not reported to health authorities, and many possible pathogens are implicated but in most cases a cause is never found. A better understanding of the epidemiology of this devastating disease will pave the way for better prevention and control strategies

A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

OBJECTIVES: To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. METHODS: The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. RESULTS: Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. CONCLUSIONS: This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis

Vaccination with complete adjuvant-added inactivated virus vaccine of Japanese encephalitis to swine, rabbits and chicks for preventing viremia (epidemiological study on Japanese encephalitis 25)

As a step towards the elimination of Japanese encephalitis virus in natural surroundings, we inoculated pigs, rabbits and chicks with inactivated Japanese encephalitis vaccine supplemented with complete or incomplete Freund's adjuvant twice at one-week interval. Subsequently, we compared HI antibody titers of the groups inoculated with vaccine containing complete Freund's adjuvant (pigs, rabbits, chicks), of the group inoculated with vaccine containing incomplete adjuvant (rabbits), ar;d of the groups inoculated with vaccine containing no adjuvant (pigs, rabbits, chicks), and also observations on changes in the antibody titers due to natural infection. In a certain portion of these animals neutralizing antibody titers were also determined. The results of this study are briefly summarized as follows. 1. In the groups of pigs and rabbits inoculated with vaccine containing complete Freund's adjuvant, titers of HI antibody and neutralizing antibody were higher than those inoculated with vaccine containing no adjuvant and their high titers persisted. Further, in the group of chicks inoculated with inactivated Japanese encephalitis vaccine containing complete Freund's adjuvant, HI antibody titers were higher and persistent as compared with the antibody titers in the chicks inoculated with inactivated Japanese encephalitis vaccine alone. 2. In the rabbits inoculated with inactivated Japanese encephalitis vaccine contammg incomplete adjuvant, HI antibody titers were lower than in those receiving the vaccine with complete adjuvant, but it has been demonstrated clearly that vaccination of inactivated Japanese encephalitis vaccine supplemented with incomplete adjuvant brings about less sideeffects. Hence such a method of vaccination can be applied as the vaccination with least side-effects. 3. With respect to natural infection of swine, on August 27 when the pigs were thought to have been infected, there was observed a rise in antibody titers. And on being infected with Japanese encephalitis, the antibodies formed in those pigs inoculated with inactivated Japanese ence- phalitis vaccine with or without complete adjuvant proved to be all 2-ME resistant type, whereas the antibodies produced in the control groups not receiving such a vaccination were 2-ME sensitive antibody.</p

Intrathecal B-cell activation in LGI1 antibody encephalitis.

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies

Acute encephalitis syndrome surveillance, Kushinagar district, Uttar Pradesh, India, 2011-2012

In India, quality surveillance for acute encephalitis syndrome (AES), including laboratory testing, is necessary for understanding the epidemiology and etiology of AES, planning interventions, and developing policy. We reviewed AES surveillance data for January 2011-June 2012 from Kushinagar District, Uttar Pradesh, India. Data were cleaned, incidence was determined, and demographic characteristics of cases and data quality were analyzed. A total of 812 AES case records were identified, of which 23\% had illogical entries. AES incidence was highest among boys<6 years of age, and cases peaked during monsoon season. Records for laboratory results (available for Japanese encephalitis but not AES) and vaccination history were largely incomplete, so inferences about the epidemiology and etiology of AES could not be made. The low-quality AES/Japanese encephalitis surveillance data in this area provide little evidence to support development of prevention and control measures, estimate the effect of interventions, and avoid the waste of public health resources

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

Coincident onset of multiple sclerosis and herpes simplex virus 1 encephalitis. a case report

Background: Along with vitamin D, smoking, body mass index and others, Epstein Barr virus, other herpesviruses and human endogenous retroviruses represent plausible environmental risk factors for multiple sclerosis. However, it is difficult to obtain direct proof of their involvement in the etiology of this condition. Case presentation: In order to contribute further evidence of the importance of these viruses, and speculate about disease-relevant interactions between these agents and a predisposed genetic background of the host, we describe the temporal association between multiple sclerosis onset and Herpes simplex 1-encephalitis in a female patient. Conclusions: This case illustrates a possible relationship between HSV-1 encephalitis and multiple sclerosis. Bearing in mind that association does not imply causation, some speculations about the etiology and pathophysiology of the two diseases can be made. The hypothesis of a genetic background predisposing to HSV-1 encephalitis and to immune-mediated demyelination is supported by the coincidence of the two conditions in this patient, along with data from animal models and genetic studies

Symptomatic treatment of children with anti-NMDAR encephalitis.

Abstract AIM: We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHOD: A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti-NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome. RESULTS: Only two out of 27 patients were white, whereas 16 out of 27 patients were from the Pacific Islands/New Zealand Maori. The mean duration of admission was 69 days (10-224d) and 48% of patients (13/27) needed treatment in an intensive care setting. A mean of eight medications per patient was used for symptomatic management. Symptoms treated were agitation (n=25), seizures (n=24), movement disorders (n=23), sleep disruption (n=17), psychiatric symptoms (n=10), and dysautonomia (n=four). The medications used included five different benzodiazepines (n=25), seven anticonvulsants (n=25), eight sedatives and sleep medications (n=23), five antipsychotics (n=12), and five medications for movement disorders (n=10). Sedative and sleep medications other than benzodiazepines were the most effective, with a mean benefit of 67.4% per medication and a mean adverse effect-benefit ratio of 0.04 per medication. Antipsychotic drugs were used for a short duration (median 9d), and had the poorest mean benefit per medication of 35.4% and an adverse effect-benefit ratio of 2.0 per medication. INTERPRETATION: Long-acting benzodiazepines, anticonvulsants, and clonidine can treat multiple symptoms. Patients with anti-NMDAR encephalitis appear vulnerable to antipsychotic-related adverse effects. Pacific Islanders appear to have a vulnerability to anti-NMDAR encephalitis in our region

Forecasting median and mode dates of prevalence of Japanese encephalitis patients by electronic computer (epidemiological studies on Japanese encephalitis, 31)

For the purpose of forecasting the prevalence ofJapanese encephalitis in Japan, we tried to find out the correlation of factors between median and mode dates of epidemic time curve of prevalence on one hand, and average atmospheric temperatures of prefectures in June and July (T6,7 in short) (X&#185;), the time when HI reaction of swine became positive to the degree of 50 per cent (D. pos. swine in short) (X&#178;), the latitude (x&#179;) and longitude (x4) in respective prefectures (in 1965 and 1967). On the other we also estimated the median and mode dates of this epidemic curve of the prevalence in 1968 and 1969, from the regression equation of one variable and multiple regression equation from the above factors using an electronic computer. The usefulness of adding factors concerned with mosquitoes to the above four factors is proven by the accuracy of estimation. And the following results were obtained. 1) Phenomenally speaking, the prevalence of Japanese encephalitis follows the principle of &#34;advancing of prevalence towards the north and east&#34; and essentially speaking, it depends upon high atmospheric temperature and the outbreak of many hazardous mosquitoes by the high atmospheric temperature. 2) To estimate median date (y) and mode rate (z) of the epidemic time curve of the prevalence, we can use the next equations; The regression equations to estimate y and z from T 6,7(X) are as follows. y = - 3. 75X&#185; + 144.47 &#963; = 12.4.·. [1] z = - 3. 80X&#185; + 157 .26 &#963; = 14.9.. · [1]' The regression equation from D. pos. swine (X&#178;) are as follows. y = 0. 68X&#178; + 31. 82 &#963; = 9.2· .. [2] z=0. 76X&#178; +40. 71 &#963;= 12.0 .. · [2]' The multiple regression equation from T6 ,7 and D. pos. swme are as follows. y = -1. 07X&#185; +0 .62x&#178; +59. 37 &#963;= 9.7 ... [3] z= -0. 79x&#185; +0. 71x&#178; +61.02 &#963;= 12.0· .. [3]' The multiple regression equations from T 6•7, D. pos. swine, latitude and longitude are as follows Y= -1.01x&#185; +0.58x&#178; -0.26x&#179;+0 .37x4 + 18.50 &#963;= 9.8&#65381;&#65381;&#65381; [4] z = -0. 32x&#185; +0. 52x&#178; +2 .05x&#179; +0 .54x4 -87. 81 &#963;= 11.8 [4]' 3) We Obtained the estimated value of median date in 17 prefectures in Kyushu, Chugoku, Shikoku, Kinki and Kanto provinces in 1968 and in 13 prefectures in 1969 from [l] or [2] or [3] or [4] equation. Nine prefectures out of 17 by [l], 12 prefectures by [2], 13 by [3J and [4] in 1968. [4] could be estimated with about 10 days error or less. And in 1969, 9 out of 13 by [3] and 7 out of 13 by [4] could be accurately esti· mated. The estimation by the multiple regression equation using many factors is most useful for the calculation. 4) The time when the number of patients increases at maximum can be pointed out by the lower limit of prediction region obtained from data in each prefecture. And the lower limit was the estimated median value minus about 20 days by [1] and about 16 days by [2] or [3] or [4] under the next condition; &#945; = 0. 1, N= 75. 5) The mode dates in 17 prefectures out of 19 were estimated by [1]', [2]', [3]' and [4]'. 12 prefectures out of 17 by [1]', 7 by [2]', 10 by [3]' and 13 by [4]' could be estimated with about 12 days error or less in 1968 and 9 out of 13 was correctly estimated by [3]' and [4]' in 1969. The estimation by the regression line of one factor was s~mewhat different from each other, but when multiple regression line of four factors was used the estimation became more correct. Judging from these results, it is adequate to use the multiple regression equation of [4] and [4]' when we want to forecast the median date or mode date ofJapanese encephalitis time cure. 6) In the case of adding two factors concerned with mosquitoes to T6,7 (X&#185;), D. pos. swine (x&#178;), latitude (x&#179;), longitude (x4), multiple regression equations become as follows. y= -1.46x&#185;+0.14X&#178;+0.068x5+89.03 &#963;= 6.9.. ·[5] z= -3. 29x&#185;+0 .13x&#178;-0. 010x5+ 143.63 &#963;= 18.6··· [5]' y=-4.20x&#185;+0.35x&#178;+0.29x6 + 53.70 &#963;= 4.2 .. ·[6] z=-2.56x&#185;-0.0lx&#178;-0.02x6 +128.96 &#963;=11.4 [6]' y= 4.76x&#185;+0.41x&#178;+0.13x5+0.22x6-72.78 &#963;= 4.5 [7] z = - 2. l0x&#185; + 0. 05x&#178;+ 0. 11 x5 - 0. 08x6+ 113.4 &#963;= 10. 7.. · [7]' where x5 is the time when the number of mosquitoes (C. T. collected by light trap reached the maximum and X6 is the time when hazardous mosq uitoes were dected. In the case of median date, 5 prefectures out of 6 prefectures by [5], 2 out of 6 by [6] and 2 out of 5 by [7], and in the case of mode date, 5 out of 6 by [5]', 4 out of 5 by [6]' and 4 out of 5 by [7]' could be accurately estimated in 1969.</p