Diagnostic approach to encephalitis and meningoencephalitis in adult returning travellers.

BACKGROUND: Encephalitis and meningoencephalitis are severe, sometime life-threatening infections of the central nervous system. Travellers may be exposed to a variety of neurotropic pathogens. AIMS: We propose to review known infectious causes of encephalitis in adults acquired outside Europe, and how to identify them. SOURCES: We used Pubmed and Embase, to search the most relevant publications over the last years. CONTENT: Microbiologic tests and radiological tools to best identify the causative pathogen in travellers presenting with encephalitis and ME are presented in this narrative review, as well as a diagnostic approach tailored to the visited area and types of exposures. IMPLICATIONS: This review highlights the diagnostic difficulties inherent to exotic causes of central nervous system infections, and attempts to guide clinicians with respect to which microbiological tests to consider, in addition to brain MRI, when approaching a returning traveller presenting with encephalitis.

Intrafamilial Transmission of Parechovirus A and Enteroviruses in Neonates and Young Infants.

BACKGROUND: Parechovirus A (PeV-A) is an important cause of sepsis and meningoencephalitis in neonates and young infants. Thus, identifying the source of PeV-A is essential for prevention; however, little is known regarding the spread of PeV-A among family members of PeV-A-infected neonates and young infants. METHODS: In this prospective study, we evaluated stool samples from family members of PeV-A-infected neonates and infants younger than 4 months who presented with sepsis, meningoencephalitis, or both in Niigata, Japan, in 2016. Because of a simultaneous outbreak, enteroviruses (EVs) were also evaluated during this period. Real-time polymerase chain reaction followed by sequence analysis was used for viral diagnosis using serum and/or cerebrospinal fluid samples. RESULTS: Among 54 febrile patients, the stool samples of 14 (26%) and 12 (22%) patients tested positive for PeV-A and EV, respectively. Stool samples from 54 family members (38 adults and 16 children) of 12 PeV-A-infected patients were available. The rate of PeV-A positivity in these samples was higher among the children (88% [14 of 16]) than the adults (34% [13 of 38]). Among family members with a PeV-A-positive stool sample, 29% (4 of 14) of the children and 77% (10 of 13) of the adults were asymptomatic. Similarly, among 53 stool samples from family members (31 adults and 22 children) of 11 EV-infected patients, the rate of EV positivity in the stool samples was higher among the children (91% [20 of 22]) than among the adults (42% [13 of 31]). The asymptomatic-patient rates were 45% (9 of 20) among the children and 85% (11 of 13) among the adults in family members with EV-positive stool. CONCLUSIONS: Similar to EVs, PeV-A was detected frequently in stool samples from family members of PeV-A-infected patients. Among family members with PeV-A-positive stool, adults were more likely than children to be asymptomatic and therefore could be an important source of PeV-A infection.

Enhanced Arboviral Surveillance to Increase Detection of Jamestown Canyon Virus Infections, Wisconsin, 2011-2016.

Jamestown Canyon virus (JCV), a mosquito-borne Orthobunyavirus (within the California serogroup), can cause severe neuroinvasive disease. According to national data during 2000-2013, 42% of the 31 documented JCV disease cases in the United States were detected in residents from Wisconsin. The Wisconsin Division of Public Health enhanced JCV surveillance by implementing routine use of JCV-specific immunoglobulin M (IgM) antibody testing followed by confirmatory JCV-specific plaque reduction neutralization testing on all patients with suspected cases of arboviral infection who had tests positive for arboviral immunoglobin at commercial laboratories. During 2011-2016, of the 287 Wisconsin specimens tested on the Arbovirus IgM Antibody Panel, 30 JCV cases were identified (26 confirmed and four probable). Twenty-seven (90%) JCV cases were detected after 2013. Among all cases, 17 (56%) were male and the median age was 54 years (range: 10-84 years). Fifteen patients had neuroinvasive disease, including meningitis (n = 9) and meningoencephalitis (n = 6). Although historically considered rare, the relatively high rate (0.12 cases/100,000 population) of diagnosis of JCV infections among Wisconsin residents during 2013-2016 compared with that in previous years suggests occurrence is widespread throughout Wisconsin and historically may have been under-recognized. This study aims to raise awareness of JCV infection for differential diagnosis among the arboviral diseases. Improved and timely diagnosis of arboviral disease is important in that it will provide more information regarding emerging infections and promote preventive measures to avoid mosquito-borne exposure and infection among residents of and visitors to affected areas.

Lymphocytic choriomeningitis virus meningoencephalitis in a renal transplant recipient following exposure to mice.

Solid organ transplant recipients (SOTR) are at increased risk for a wide variety of typical and atypical infections as a consequence of impaired cell mediated and humoral immunity. We report a case of meningoencephalitis in a renal transplant recipient caused by lymphocytic choriomeningitis virus (LCMV) acquired by exposure to mice excreta. The clinical course was complicated by the development of hydrocephalus, requiring a ventriculoperitoneal shunt. To our knowledge, this is the first reported case of LCMV infection in a SOTR that was not organ donor derived.

[Zika virus infection and the nervous system]. / Zika-Virus-Infektion und das Nervensystem.

Zika virus is an arbovirus from the family of flaviviruses, which is transmitted by the mosquito Aedes aegyptii and also by the Asian mosquito Aedes albopticus. The largest observed Zika virus epidemic is currently taking place in North and South America, in the Caribbean, southern USA and Southeast Asia. In most cases the infection is an unspecific, acute, febrile disease. Neurological manifestations consist mainly of microcephaly in newborns and Guillain-Barré syndrome but other rare manifestations have also become known in the meantime, such as meningoencephalitis and myelitis. Therefore, the Zika virus, similar to other flaviviruses, has neuropathogenic properties. In particular, the drastic increase in microcephaly cases in Brazil has induced great research activities. The virus is transmitted perinatally and can be detected in the amniotic fluid, placenta and brain tissue of the newborn. Vaccination or a causal therapy does not yet exist. The significant increase in Guillain-Barré syndrome induced by the Zika virus was observed during earlier outbreaks. In the meantime, scientifically clear connections between a Zika virus infection and these neurological manifestations have been shown. Long-term studies and animal models should be used for a better understanding of the pathomechanisms of this disease.

Situación epidemiológica de las meningoencefalitis bacterianas / Epidemiological situation of bacterial meningoencephalitis

Se describen los casos de meningoencefalitis bacterianas exponiendo el análisis histórico de algunas variables y a continuación la información desde la Semana epidemiológica (SE) 1 a la 25 del año 2017 que provienen de la notificación por canales oficiales: SNVS (módulos C2/SIVILA) y SIC (Sistema de Información epidemiológica de CABA). El análisis de las infecciones invasivas no meníngeas será realizado en próximas actualizaciones. Los casos fueron notificados a través de estos sistemas por los efectores públicos y privados de la Ciudad. El análisis de los mismos se realizó de manera individual a fin de evitar duplicaciones, excluyendo los casos descartados e integrando la información en una base unificada. Se incluyeron como residentes de CABA a todos aquellos que se domicilian en la Ciudad y aquellos casos atendidos en efectores de la CABA cuyo domicilio es desconocido al momento del análisis. La construcción de las tasas, se realizó en base a las proyecciones poblacionales aportadas por la Dirección de Estadística y Censos (DGEyC) de la Ciudad Autónoma de Buenos Aires. (AU)

Bovine herpesvirus type 5 in semen samples from bulls in Iran.

Bovine herpesvirus 5 (BoHV-5) is an important pathogen of the central nervous system and has already been described in the genital tract of cattle and in semen. This virus is responsible for sporadic epizootics of fatal meningoencephalitis of calves. The objective of the present study was the identification and characterization of BoHV-5 in semen samples from bulls for the first time in Iran. DNA was extracted from bull semen samples, and the glycoprotein D (gD) gene of BoHV-5 and also the thymidine kinase (tK) gene of bovine herpesvirus 1 (BoHV-1) were amplified by PCR assay. The results showed a high prevalence of BoHV-5 (73.2 %) and BoHV-1 (25.89 %) in Iranian bull semen samples. In addition, in order to identify and compare BoHV-5 isolated from Iranian bulls with other isolates from all over the world, the gD gene of this virus was cloned and sequenced. A BLAST search showed that the sequence of the gD gene of BoHV-5 from Iran was 99 % identical to other sequences in the GenBank database. The present study indicated that semen samples are important transmission sources of BoHV-5 virus in Iranian bulls.

Detection of donor-derived CMV-specific T cells in cerebrospinal fluid in a case of CMV meningoencephalitis after cord blood stem cell transplantation.

Cytomegalovirus (CMV) meningoencephalitis is a rather rare complication after allogeneic stem cell transplantation. We describe here the case of a 59-year-old man with acute myeloid leukemia who developed CMV meningoencephalitis after cord blood transplantation. The patient presented with a sudden onset of neurological symptoms, such as convulsion, on day 37. The analysis of cerebrospinal fluid (CSF) sample revealed an increase in the number of cells, which were of donor (cord blood) origin, consisting mainly of T cells. No bacteria were detected in the CSF sample. Real-time PCR analysis revealed that the CSF sample was positive for CMV, but was negative for HHV-6, adenovirus, or BK virus. The patient was diagnosed with CMV meningoencephalitis and received cidofovir. His neurological symptoms were gradually improved and completely disappeared by day 60. CMV-specific dextramer-positive CD8(+) T cells were detected in the peripheral blood and CSF samples, with the frequency being much higher in the CSF. To our knowledge, this is the first report on the appearance of CMV-specific T cells in CSF samples from a patient with CMV meningoencephalitis. Cord blood-derived CMV-specific T cells may develop early after transplantation, enter the intrathecal compartment, and likely contribute to the regulation of CMV-meningoencephalitis.

MRI findings in acute Hendra virus meningoencephalitis.

AIM: To describe serial changes in brain magnetic resonance imaging (MRI) in acute human infection from two outbreaks of Hendra virus (HeV), relate these changes to disease prognosis, and compare HeV encephalitis to reported cases of Nipah virus encephalitis. MATERIALS AND METHODS: The MRI images of three human cases (two of which were fatal) of acute HeV meningoencephalitis were reviewed. RESULTS: Cortical selectivity early in the disease is evident in all three patients, while deep white matter involvement appears to be a late and possibly premorbid finding. This apparent early grey matter selectivity may be related to viral biology or ribavirin pharmacokinetics. Neuronal loss is evident at MRI, and the rate of progression of MRI abnormalities can predict the outcome of the infection. In both fatal cases, the serial changes in the MRI picture mirrored the clinical course. CONCLUSION: This is the first comprehensive report of serial MRI findings in acute human cerebral HeV infection from two outbreaks. The cortical selectivity appears to be an early finding while deep white matter involvement a late, and possibly premorbid, finding. In both fatal cases, the serial changes in MRI mirrored the clinical course.

Comparative study on the in vitro and in vivo properties of two bovine herpesvirus-5 reference strains.

BACKGROUND: Bovine herpesvirus 5 (BoHV-5) is an alphaherpesvirus responsible for meningoencephalitis in young cattle and it is antigenically and genetically related to bovine herpesvirus 1. BoHV-5 outbreaks are sporadic and restricted in their geographical distribution, being mostly detected in the Southern hemisphere. The N569 and A663 strains are prototypes of the "a" and "b" subtypes of BoHV-5, however, scarce information about their in vitro and in vivo properties is currently available. METHODS: For the in vitro comparison between BoHV-5 A663 and N569 strains, viral growth kinetics, lysis and infection plaque size assays were performed. Additionally, an experimental infection of cattle with BoHV-5 A663 and N569 strains was carried out. Viral excretion, development of neurological signs, presence of specific antibodies in serum and nasal swabs and presence of latent BoHV-5 DNA in trigeminal ganglion, were analyzed. Histopathological examination of samples belonging to inoculated animals was also performed. RESULTS: The lytic capacity and the cell-to-cell spread was lower for the A663 strain compared to the N569 strain, however, the production of total infectious viral particles was similar between both strains. Concerning the in vivo properties, the A663 and N569 strains are able to induce similar degrees of pathogenicity in cattle. CONCLUSIONS: Our results show that the A663 strain used in this study is less adapted to in vitro replication in MDBK cells than the N569 strain and, although slight differences were observed, both strains are able to induce a similar degree of virulence in the natural host.

First report of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Achatina fulica (Mollusca: Gastropoda) from Southeast and South Brazil.

The rat lungworm Angiostrongylus cantonensis is a worldwide-distributed zoonotic nematode that can cause human eosinophilic meningoencephalitis. Here, for the first time, we report the isolation of A. cantonensis from Achatina fulica from two Brazilian states: Rio de Janeiro (specifically the municipalities of Barra do Piraí, situated at the Paraiba River Valley region and São Gonçalo, situated at the edge of Guanabara Bay) and Santa Catarina (in municipality of Joinville). The lungworms were identified by comparing morphological and morphometrical data obtained from adult worms to values obtained from experimental infections of A. cantonensis from Pernambuco, Brazil, and Akita, Japan. Only a few minor morphological differences that were determined to represent intra-specific variation were observed. This report of A. cantonensis in South and Southeast Brazil, together with the recent report of the zoonosis and parasite-infected molluscs in Northeast Brazil, provide evidence of the wide distribution of A. cantonensis in the country. The need for efforts to better understand the role of A. fulica in the transmission of meningoencephalitis in Brazil and the surveillance of molluscs and rodents, particularly in ports, is emphasized.

First report of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Achatina fulica (Mollusca: Gastropoda) from Southeast and South Brazil

The rat lungworm Angiostrongylus cantonensis is a worldwide-distributed zoonotic nematode that can cause human eosinophilic meningoencephalitis. Here, for the first time, we report the isolation of A. cantonensis from Achatina fulica from two Brazilian states: Rio de Janeiro (specifically the municipalities of Barra do Piraí, situated at the Paraiba River Valley region and São Gonçalo, situated at the edge of Guanabara Bay) and Santa Catarina (in municipality of Joinville). The lungworms were identified by comparing morphological and morphometrical data obtained from adult worms to values obtained from experimental infections of A. cantonensis from Pernambuco, Brazil, and Akita, Japan. Only a few minor morphological differences that were determined to represent intra-specific variation were observed. This report of A. cantonensis in South and Southeast Brazil, together with the recent report of the zoonosis and parasite-infected molluscs in Northeast Brazil, provide evidence of the wide distribution of A. cantonensis in the country. The need for efforts to better understand the role of A. fulica in the transmission of meningoencephalitis in Brazil and the surveillance of molluscs and rodents, particularly in ports, is emphasized.

Isolation of bovine herpesvirus type 5 from the semen of a healthy bull in Australia.

Artificial insemination is widely used in the cattle industry and a major challenge is to ensure that semen is free of infectious agents. A healthy donor bull was tested for freedom from infectious agents. A bovine herpesvirus was isolated in testis cells and identified as bovine herpesvirus type 5 (BoHV-5) by polymerase chain reaction and by direct amplicon sequencing. The amplicon sequence shared 100% similarity with the published sequence of BoHV-5. This is the first report in Australia of BoHV-5 in semen. The implications of this finding are discussed.

Tick-borne encephalitis.

In middle and eastern European countries, tick-borne encephalitis (TBE) is one of the most important human infections of the central nervous system. TBE virus (TBEV) is mainly transmitted by tick bites and rarely by unpasteurized milk. In European countries, TBE presents as meningitis in about 50% of patients, as meningoencephalitis in 40%, and as meningoencephalomyelitis in 10%. The severity of TBE increases with age; in children and adolescents, meningitis is the predominant form of the disease. The long-term prognosis is unfavorable in about 40% to 50% of patients who sustain sequelae for months to years, mainly in terms of pareses, ataxia, and other gait disturbances. No specific treatment for TBE is known. It can be successfully prevented by active immunization.

Tuberculous meningoencephalitis in a wild boar.

Bovine tuberculosis, caused by Mycobacterium bovis, is a zoonotic disease that affects cattle and wildlife worldwide. These animal hosts can serve as reservoirs of infection, thus increasing the risk of human exposure and infection. Tuberculous meningoencephalitis complicating disseminated tuberculosis is described in a 7-mo-old wild boar (Sus scrofa).

Simultaneous tuberculous meningoencephalitis in two siblings.

UNLABELLED: The high morbidity and mortality of tuberculous meningoencephalitis (TBM) warrants an early diagnosis and treatment. BCG vaccine has been proven to reduce the incidence of disseminated disease in children. We report on two siblings (2-year-old boy and 4-year-old girl) with simultaneous TBM, whose parents originated from Kosovo, Albania, but presently reside in Germany. Early diagnosis of TBM was delayed, and at first the misdiagnosis of viral meningoencephalitis was made. Antituberculosis treatment was not initiated despite profound hyponatremia, hydrocephalus, and signs of inflammatory cerebral disease. After establishing the diagnosis of TBM, the boy died from antituberculosis, drug-induced hepatic failure; the sister survived with severe neurological deficits. Contact tracing revealed that TB had been transmitted by a household contact person with proven pulmonary TB who had refused antituberculosis treatment. A thorough contact investigation including tuberculin skin testing to identify children at risk for TB in the vicinity of this patient was not carried out. These case reports demonstrate an unusual simultaneous occurrence of TBM in a brother and sister. It draws attention to the importance of TBM as a differential diagnosis in children with suspected viral meningoencephalitis. CONCLUSIONS: To prevent severe neurological sequelae, early antituberculosis therapy should be considered in infants and children with a clinical impression of meningitis in the context of cerebrospinal fluid white blood cell count of less than 500 cells/microl and lymphocytic predominance, hyponatremia, and possible hydrocephalus. This notion is especially true for children originating from high-endemicity countries for TB. A rigid implementation of antituberculosis treatment of infected individuals and contact tracing is mandatory in order to prevent dissemination of TB in the community. The use of BCG vaccine should be considered in children at high risk for TB infection because of its potential to reduce disseminated TB.