Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden

An estimate of Lyme borreliosis incidence in Western Europe

Background: Lyme borreliosis (LB) is the most common zoonotic disease transmitted by ticks in the USA and Europe. This review aims to estimate the regional burden of LB in Western Europe. Data from previous publications will be used to calculate the mean incidence. The mean incidence rates will then be combined to estimate the regional burden and a population-weighted regional burden of disease based on the standardized incidence rate from the included studies and the total population at risk. Methods: Reviews and surveillance reports identified by the initial database search were assessed for eligibility first by their title and abstract and subsequently by a more detailed review of the source by two independent authors for the most recent data regarding LB. Eleven sources of incidence data were included in the review representing 17 countries in total. Incidence estimates were calculated from reported values and population data. Results: Countries in Western Europe have a large variance in the incidence rates. The highest reported incidences for LB were reported in southern Sweden with 464/100 000 and the lowest in Italy of 0.001/100 000. The unweighted mean for the included data provided an incidence rate of 56.3/100 000 persons per year, equating to ∼232 125 cases in 1 year throughout the region. The calculated population-weighted average incidence rate for the regional burden of LB in Western Europe was 22.05 cases per 100 000 person-years. Conclusions: LB is a continually emerging disease and the most common zoonotic infection in Western Europe approaching endemic proportions in many European countries. The population-weighted incidence rate has been estimated by this study to be 22.04/100 000 person-years. Concordant and well-conducted surveillance and disease awareness should continue to be encouraged to monitor LB, as tick numbers and activity are increasing, leading to greater risks of infection

Comorbidities and predictors of health-related quality of life in Dravet syndrome: a ten-year prospective follow- up study

Objective: Dravet Syndrome (DS) is a severe developmental and epileptic encephalopathy, leading to reduced health related quality of life (HRQOL). Prospective outcome data on HRQOL are sparse and this study investigated long-term predictors of HRQOL in DS. Methods: 113 families of SCN1A-positive DS patients recruited as part of our 2010 study were contacted at 10-year follow-up, of which 68 (60%) responded. The mortality was 5.8%. Detailed clinical and demographic information was available for each patient. HRQOL was evaluated with two epilepsy-specific instruments, the Impact of Pediatric Epilepsy Scale (IPES) and the Epilepsy & Learning Disabilities Quality of Life Questionnaire (ELDQOL); a generic HRQOL instrument, the Pediatric Quality of Life Inventory (PedsQL); and a behavioral screening tool, the Strength and Difficulties Questionnaire (SDQ). Results: Twenty-eight patients were aged 10-15 years (0-5 years at baseline) and 40 were aged ≥16 years (≥6 years at baseline). Patients 0-5 years old at baseline showed significant decline in mean scores on the PedsQL total score (p=0.004), physical score (p<0.001), cognitive score (p=0.011), social score (p=0.003), and eating score (p=0.030) at follow-up. On multivariate regression, lower baseline and follow-up HRQOL for the whole cohort were associated with worse epilepsy severity and a high SDQ total score (R2=33% and 18% respectively). In the younger patient group, younger age at first seizure and increased severity of epilepsy were associated with a lower baseline HRQOL (R2=35%). In the older age group, worse epilepsy severity (F=6.40, p=0.016, R2=14%) and the use of sodium-channel blockers were independently associated with a lower HRQOL at 10-year follow-up (F=4.13, p=0.05, R2=8%). Significance: This 10-year prospective follow-up study highlights the significant HRQOL-associated cognitive, social and physical decline particularly affecting younger patients with DS. Sodium channel blocker use appears to negatively impact long-term HRQOL highlighting the importance of early diagnosis and disease specific management in DS