Upsurge in echovirus 30 detections in five EU/EEA countries, April to September, 2018

An upsurge in Echovirus 30 (E30) infections, associated with meningitis/meningoencephalitis, has been observed in Denmark, Germany, the Netherlands, Norway and Sweden in the period April to September 2018, compared with 2015–2017. In total, 658 E30 infections among 4,537 enterovirus infections were detected in 15 countries between January and September 2018 and affected mainly newborns and 26–45 year-olds. National public health institutes are reminded to remain vigilant and inform clinicians of the ongoing epidemic.


Table 1a
Type of data and number of enterovirus and echovirus 30 infections reported by country in the EU/EEA, January-September, 2018 (n = 4,537) Countries who report on the age, sex and detailed symptom data for enteroviruses, but did not have any E30 cases to report on, have been marked as NA.
b An active surveillance system was defined as a system that is based on the public health officials› initiative to contact the physicians, laboratory or hospital staff or other relevant sources to report data. Passive surveillance was defined as a system relying on the physicians, laboratory or hospital staff or other relevant sources to take the initiative to report data to the health department [4].  Countries who report on the age, sex and detailed symptom data for enteroviruses, but did not have any E30 cases to report on, have been marked as NA.
b An active surveillance system was defined as a system that is based on the public health officials› initiative to contact the physicians, laboratory or hospital staff or other relevant sources to report data. Passive surveillance was defined as a system relying on the physicians, laboratory or hospital staff or other relevant sources to take the initiative to report data to the health department [4]. in the country also perform EV molecular detection in suspected cases; typing is not performed routinely for these cases; these data are not available at the moment.

Table 1c
Type a Countries who report on the age, sex and detailed symptom data for enteroviruses, but did not have any E30 cases to report on, have been marked as NA.
b An active surveillance system was defined as a system that is based on the public health officials› initiative to contact the physicians, laboratory or hospital staff or other relevant sources to report data. Passive surveillance was defined as a system relying on the physicians, laboratory or hospital staff or other relevant sources to take the initiative to report data to the health department [4].  Countries who report on the age, sex and detailed symptom data for enteroviruses, but did not have any E30 cases to report on, have been marked as NA.
b An active surveillance system was defined as a system that is based on the public health officials› initiative to contact the physicians, laboratory or hospital staff or other relevant sources to report data. Passive surveillance was defined as a system relying on the physicians, laboratory or hospital staff or other relevant sources to take the initiative to report data to the health department [4]. Austria submitted enterovirus detections by quarter ( Figure 2). The proportion of E30 detections among the enterovirus-positive samples was at its lowest in May (7%; 27/407 EVs), increased to 14% (81/575) in June and further to 18% (99/564) in July, and returned to 11% in August (69/611) ( Figure 2). The proportion of E30 infections among typed enteroviruses in July was 37% for the Netherlands and 29% for Sweden. Those two countries submitted number of typed enteroviruses instead of total number of enterovirus-positive samples.

Comparison of 2018 findings with data from 2015 to 2017
We compared the 2018 counts of E30 detections with data for the period 2015 to 2017, reported through an unpublished ECDC survey (data not shown). Data from a country were included if more than 10 E30 detections were reported for the period 2015 to 2017 and if the country responded to our data call. Nine of 15 participating countries were included in this analysis. Based on the available data, a more than twofold increase in detections was shown for Denmark from May to July and in September, for Germany from June to August, for the Netherlands from April to September, for Norway from July to September and for Sweden from June to September 2018, compared with the respective monthly average of E30 detections during 2015 to 2017 ( Figure 3). Based on the data from 2015 to 2017, the UK experienced a marked increase of E30 detections in July and October 2017 that continued until February See Table 1 for details on the countries. Austria reported data by quarter (n=3 in the period from April to June); for the purposes of this graph, we display them as 1 case per month in that quarter. Austria subsequently reported an additional two E30 infections for June, and therefore the total count for June is three. The Czech Republic and Slovenia did not detect any E30 between January and September 2018 and are therefore not included in the figure.
2018, but has not observed an increase in summer 2018 ( Figure 3). The Czech Republic experienced an increase in July 2016 and Denmark, the Netherlands, Norway and Sweden in October 2017.
The main age groups affected by the E30 infections in 2018 were newborns under the age of 3 months and adults aged 26-45 years (

Discussion
From April to September 2018, an increase in E30 infections, associated with cases of meningitis and meningoencephalitis, has been detected in five countries in the EU/EEA, compared with previous years.
E30 is an enterovirus of the B species that causes aseptic meningitis, often associated with outbreaks, some of which have been large [6][7][8][9][10]. Aseptic meningitis is the most commonly reported syndrome associated with E30 infections [8][9][10][11]. Although non-polio enterovirus infections are usually benign and self-limiting, they can also cause more severe, life-threatening diseases (e.g. encephalitis, paralysis, myopericarditis  and neonatal enteroviral sepsis) [7]. The majority of the patients recover with symptomatic treatment within one week.
E30 epidemics occur usually as repeated cycles of emerging and dominating virus lineages that cause outbreaks every 3-5 years, often covering large geographical areas, and disappear thereafter to re-emerge later [12]. In the United States, E30 has caused outbreaks at irregular intervals but with a duration of several years [13]. In Europe, several countries have in recent years reported increased incidence of E30: Austria in 2000 [14], Spain from 2000 to 2002 [15], France in 2005 [16], Germany in 2008 [17], Finland from 2009 to 2010 [18,19], Latvia and Serbia in 2010 [20,21], Greece in 2012 [22] and France and Germany in 2013 [17,23]. In these outbreaks, E30 was detected mainly in children younger than 15 years [9,[21][22][23] but also in adults [8,13]. Enteroviruses usually spread through personto-person transmission via the faecal-oral or oral-oral route. However, echovirus outbreaks associated with swimming pools [24,25] as well as nature-like ponds [11] have been reported.
Based on the available data, five EU/EEA countries (Denmark, Germany, the Netherlands, Norway and Sweden) experienced or are still experiencing an E30 upsurge during summer and autumn 2018 compared with the same months of previous years. The current upsurges affected in particular newborns and adults aged 26-45 years of both sexes but with a predominance of males. The majority (75%) of reported patients experienced CNS symptoms, mainly meningitis or meningoencephalitis. In at least two of these countries, detection of upsurges and reporting of cases was particularly focused on patients with CNS symptoms and such cases are therefore likely to be over-represented.
When interpreting the data, the following limitations have to be considered: firstly, enterovirus surveillance is mainly passive and therefore captures primarily viruses isolated from severe cases rather than from patients with mild diseases. This may skew the results towards severe outcomes even in the countries that have access to clinical information. Secondly, only 15 EU/EEA countries took part in the study and the data are therefore not representative for the whole EU/EEA region. Four countries also indicated that their data were not from all parts of the country and five that the data were not representative for the entire population or that representativeness was unknown. We also acknowledge that the level of testing and methods used for diagnostics and typing vary between the countries and may affect the sensitivity of detection and typing.
Thirdly, some E30 results may have been missed with the regularly used VP1 sequence typing protocol [5] because of low viral load in the initial specimen, especially if CSF or serum was sent to the laboratory without an additional stool specimen, which is preferred. It also needs to be considered that some typing data were still pending for August and September as at 22 October. Fourthly, data were collected in aggregate format by age group, sex and clinical symptom and therefore no further analysis could be performed on specific age groups and clinical symptoms or sex ratio. Finally, to further assess the extent of the E30 upsurge in 2018 compared with earlier epidemics, longer data series would have been beneficial.
Specific prevention and control measures are not available for E30. Good hygiene practices such as frequent hand washing, avoidance of shared utensils, bottles or glasses and disinfection of contaminated surfaces (e.g. with diluted bleach solution) are recommended to prevent the spread of E30 from person to person. Further spread in the affected countries cannot be excluded and the non-affected countries or countries where enterovirus surveillance is lacking or not covering the whole population should remain vigilant for non-polio enterovirus outbreaks. It has been shown that considerable health resources can be saved by rapid detection of the virus [22], dissemination of information about the epidemics and a conservative approach to clinical management [26]. Differential diagnostics of viruses in meningitis cases may also prevent unnecessary use of antibiotics. As the epidemic is still ongoing in several countries, clinicians need to be made aware by national health authorities of this recent increase in E30 infections. Overall, EU/EEA countries have good coverage for detection of non-polio enteroviruses through their enterovirus surveillance systems [3]. For detection, technical recommendations are available from the European non-polio enterovirus network (ENPEN) [27]. It is also important for awareness raising that the countries share their data on enterovirus epidemics e.g. through the Epidemic Intelligence System (EPIS) and ENPEN to further understand the circulation and impact of non-polio enterovirus infections in Europe. As the E30 activity can last several years, it is relevant to consider preparedness for the 2019 season.
This study has shown that the public health networks across EU/EEA can share their clinical and public health surveillance, and diagnostic laboratory data on emerging enterovirus infections ad hoc and in a timely fashion. Genetic analysis is ongoing and will shed light on whether the virus strain causing the increase in Europe is similar to previous years or novel. In addition, epidemiological investigations by the Member States will help understand the transmission patterns.