Molecular surveillance of measles and rubella in the WHO European Region: new challenges in the elimination phase.

BACKGROUND: The WHO European Region (EUR) has adopted the goal of eliminating measles and rubella but individual countries perform differently in achieving this goal. Measles virus spread across the EUR by mobile groups has recently led to large outbreaks in the insufficiently vaccinated resident population. As an instrument for monitoring the elimination process and verifying the interruption of endemic virus transmission, molecular surveillance has to provide valid and representative data. Irrespective of the country's specific situation, it is required to ensure the functionality of the laboratory surveillance that is supported by the WHO Global Measles and Rubella Laboratory Network. AIMS: To investigate whether the molecular surveillance in the EUR is adequate for the challenges in the elimination phase, we addressed the quality assurance of molecular data, the continuity and intensity of molecular monitoring, and the analysis of transmission chains. SOURCES: Published articles, the molecular External Quality Assessment Programme of the WHO, the Centralized Information System for Infectious Diseases of the WHO EUR and the WHO Measles and Rubella Nucleotide Surveillance databases served as information sources. CONTENT: Molecular proficiency testing conducted by the WHO in 2016 has shown that the expertise for measles and rubella virus genotyping exists in all parts of the EUR. The analysis of surveillance data reported nationally to the WHO in 2013-2016 has revealed some countries with outbreaks but not sufficiently representative molecular data. Long-lasting supranational MV transmission chains were identified. IMPLICATIONS: A more systematic molecular monitoring and recording of the transmission pattern for the whole EUR could help to create a meaningful picture of the elimination process.

European survey on laboratory preparedness, response and diagnostic capacity for Crimean-Congo haemorrhagic fever, 2012.

Crimean-Congo haemorrhagic fever (CCHF) is an infectious viral disease that has (re-)emerged in the last decade in south-eastern Europe, and there is a risk for further geographical expansion to western Europe. Here we report the results of a survey covering 28 countries, conducted in 2012 among the member laboratories of the European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) to assess laboratory preparedness and response capacities for CCHF. The answers of 31 laboratories of the European region regarding CCHF case definition, training necessity, biosafety, quality assurance and diagnostic tests are presented. In addition, we identified the lack of a Regional Reference Expert Laboratory in or near endemic areas. Moreover, a comprehensive review of the biosafety level suitable to the reality of endemic areas is needed. These issues are challenges that should be addressed by European public health authorities. However, all respondent laboratories have suitable diagnostic capacities for the current situation.

Usutu virus: potential risk of human disease in Europe.

Usutu virus (USUV) is an African mosquito-borne flavivirus, member of the Japanese encephalitis antigenic group. This avian virus is transmitted by arthropod vectors (mainly mosquitoes of the Culex pipiens complex). It is well known that free-living birds, including migratory species, have the potential to disperse certain pathogenic microorganisms. Usutu virus has recently been introduced to Europe and is spreading through Austria, Hungary, Italy, Spain and Switzerland, causing disease in birds and humans. Like West Nile virus, USUV may become a resident pathogen in Europe and the consequences for public health should be considered. Many different biotic and abiotic factors affect the survival of the virus in a new environment and influence the efficiency of its geographical dispersal. In this article, we consider the possibility of including USUV infections among the vector-borne diseases to be monitored in Europe.

International diagnostic accuracy study for the serological detection of chikungunya virus infection.

External quality assurance for serological detection of chikungunya virus infection was performed to assess the diagnostic quality of expert laboratories. Of 30 participants, only six correctly analysed all reference samples with their respective tests. Thirteen laboratories gave at least 85% correct results, and 11 laboratories 75% or less. IgM antibodies were detected less frequently than IgG antibodies (p <0.001). The study provides information on the quality of different serological tests and indicates that most of the participants need to improve the sensitivity of their assays, in particular to detect IgM antibodies more reliably and be able to detect acute infections adequately.

Analysis of the surveillance situation for viral encephalitis and meningitis in Europe.

Infective processes in the brain, spinal cord and meninges are considered to be the main causes of encephalitis, myelitis and meningitis. However, most cases remain unexplained. The incidence of different viral aetiologies (zoonotic and non-zoonotic) is especially poorly estimated, due to the lack of a standard case definition and of agreed diagnostic algorithms, including harmonised diagnostic methods and sample collection. It is important to clarify the incidence of viral encephalitis/meningitis and to optimise the diagnosis of infectious neurological illness, particularly to ensure early recognition of outbreaks or emerging infectious such a West Nile encephalitis. The European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) has analysed the present surveillance situation for viral encephalitis/meningitis in Europe. Here we give an overview of the existing epidemiological sources of information in European Union (EU) Member States, mapping the laboratory capacity and identifying key requirements for a possible future surveillance study at European level. The data presented will help design a harmonised/standardised Europe-wide surveillance study investigating patients with encephalitis and/or meningitis in order to obtain more information on the role of infections in these rarely analysed syndromes, both from a clinical and an epidemiological perspective.

A survey on cases of tick-borne encephalitis in European countries.

The European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) is finalising a project to improve the diagnostic and monitoring of encephalitis viruses in Europe. Part of this study was to analyse the present surveillance situation for tick-borne encephalitis (TBE), which is the most important flavivirus infection of the central nervous system in the European Union (EU) and Russia. A questionnaire was mailed to contact points in all Member States of the EU and three non-EU countries (Norway, Russia and Switzerland) to summarise their TBE surveillance and prevention activities. Information was requested on case definition, type of laboratory tests for TBE diagnostics, investigations regarding tick-transmitted diseases, mapping of endemic foci, vaccination programmes, and recommendations for travellers. The survey gives an overview of the existing epidemiological and laboratory sources of information and the number of TBE cases from 2004 until 2007, but also showed that, in particular, case definitions, diagnostic assays for confirmation, and methods/indicators for mapping risk areas differ widely across the participating countries. The data will help to develop recommendations for the standardisation and quality control or TBE surveillance and diagnostics.

Quality assurance for the diagnostics of viral diseases to enhance the emergency preparedness in Europe.

The threat posed by emerging and re-emerging communicable diseases and, more recently, by the intentional release of infectious agents in a susceptible population, has been receiving considerable attention at the national and international levels. Public health efforts to strengthen disease detection, surveillance and control have been intensified. However, clinicians and clinical microbiology laboratories play an important role in the early detection of disease, the identification of the putative agent, and notification of the appropriate authorities. To be effective in this role, laboratories must be specially prepared to handle viral agents safely, and need, among other things, the appropriate rapid and sensitive diagnostic tests. In 1998 the European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) was established. ENIVD presently comprises, as permanent members, 44 expert laboratories in 21 European Union (EU) member states and 4 non-EU countries and is one of the networks on infectious diseases funded by the European Commission. ENIVD fulfils many of the important tasks required for the surveillance and control of imported, rare and emerging viral infections such as the exchange of expertise and the organisation of external quality assurance (EQA) programmes, both of which are needed to improve diagnostics. Here, we summarise the data generated by recent EQA activities focussed on the diagnostics of infections with hantavirus, dengue virus, filovirus, Lassa virus, orthopox virus and the SARS-coronavirus (SARS-CoV). These were carried out between 1999 and 2004 and involved 93 laboratories from 41 countries, including laboratories from additional countries outside of Europe. Particularly the EU-candidate countries and Eastern neighbouring countries will be invited to join the network in the near future. A public website is available at http://www.enivd.de.

Susceptibility of different eukaryotic cell lines to SARS-coronavirus.

In order to define and characterize target cells of SARS-coronavirus (SARS-CoV) we studied the susceptibility of 23 different permanent and primary eukaryotic cell lines to SARS-coronavirus. Beneath Vero E6 cells SARS- Coronavirus infection could also be demonstrated in two pig cell lines (POEK, PS) and one human cell line (Huh-7) using the indirect immunofluorescence assay and a newly established quantitative real-time PCR. In all susceptible cell lines mRNA of the Angiotensin-converting enzyme 2 (ACE2), the functional receptor for SARS-CoV infection, could be detected by RT-PCR. Our results show that there is a correlation between the abundance of ACE2 mRNA and SARS-CoV susceptibility.

Quality assurance for the diagnostics of viral diseases to enhance the emergency preparedness in Europe.

The threat posed by emerging and re-emerging communicable diseases and, more recently, by the intentional release of infectious agents in a susceptible population, has been receiving considerable attention at the national and international levels. Public health efforts to strengthen disease detection, surveillance and control have been intensified. However, clinicians and clinical microbiology laboratories play an important role in the early detection of disease, the identification of the putative agent, and notification of the appropriate authorities. To be effective in this role, laboratories must be specially prepared to handle viral agents safely, and need, among other things, the appropriate rapid and sensitive diagnostic tests. In 1998 the European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) was established. ENIVD presently comprises, as permanent members, 44 expert laboratories in 21 European Union (EU) member states and 4 non-EU countries and is one of the networks on infectious diseases funded by the European Commission. ENIVD fulfils many of the important tasks required for the surveillance and control of imported, rare and emerging viral infections such as the exchange of expertise and the organisation of external quality assurance (EQA) programmes, both of which are needed to improve diagnostics. Here, we summarise the data generated by recent EQA activities focussed on the diagnostics of infections with hantavirus, dengue virus, filovirus, Lassa virus, orthopox virus and the SARS-coronavirus (SARS-CoV). These were carried out between 1999 and 2004 and involved 93 laboratories from 41 countries, including laboratories from additional countries outside of Europe. Particularly the EU-candidate countries and Eastern neighbouring countries will be invited to join the network in the near future. A public website is available at http://www.enivd.de.