The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

BACKGROUND: Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. METHODS: We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. RESULTS: Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. CONCLUSIONS: The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

Targeting of blood safety measures to affected areas with ongoing local transmission of malaria.

An outbreak of locally acquired Plasmodium vivax malaria in Greece started in 2009 and peaked in 2011. Targeting of blood safety measures to affected areas with ongoing transmission of malaria raised questions of how to define spatial boundaries of such an area and when to trigger any specific blood safety measures, including whether and which blood donation screening strategy to apply. To provide scientific advice the European Centre for Disease Prevention and Control (ECDC) organised expert meetings in 2013. The outcomes of these consultations are expert opinions covering spatial targeting of blood safety measures to affected areas with ongoing local transmission of malaria and blood donation screening strategy for evidence of malaria infection in these areas. Opinions could help EU national blood safety authorities in developing a preventive strategy during malaria outbreaks.

An entomological review of invasive mosquitoes in Europe.

Among the invasive mosquitoes registered all over the world, Aedes species are particularly frequent and important. As several of them are potential vectors of disease, they present significant health concerns for 21st century Europe. Five species have established in mainland Europe, with two (Aedes albopictus and Aedes japonicus) becoming widespread and two (Ae. albopictus and Aedes aegypti) implicated in disease transmission to humans in Europe. The routes of importation and spread are often enigmatic, the ability to adapt to local environments and climates are rapid, and the biting nuisance and vector potential are both an ecomonic and public health concern. Europeans are used to cases of dengue and chikungunya in travellers returning from the tropics, but the threat to health and tourism in mainland Europe is substantive. Coupled to that are the emerging issues in the European overseas territorities and this paper is the first to consider the impacts in the remoter outposts of Europe. If entomologists and public health authorities are to address the spread of these mosquitoes and mitigate their health risks they must first be prepared to share information to better understand their biology and ecology, and share data on their distribution and control successes. This paper focusses in greater detail on the entomological and ecological aspects of these mosquitoes to assist with the risk assessment process, bringing together a large amount of information gathered through the ECDC VBORNET project.

Laboratory capability and surveillance testing for Middle East respiratory syndrome coronavirus infection in the WHO European Region, June 2013.

Since September 2012, over 90 cases of respiratory disease caused by a novel coronavirus, now named Middle East respiratory syndrome coronavirus (MERSCoV), have been reported in the Middle East and Europe. To ascertain the capabilities and testing experience of national reference laboratories across the World Health Organization (WHO) European Region to detect this virus, the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe conducted a joint survey in November 2012 and a follow-up survey in June 2013. In 2013, 29 of 52 responding WHO European Region countries and 24 of 31 countries of the European Union/European Economic Area (EU/EEA) had laboratory capabilities to detect and confirm MERS-CoV cases, compared with 22 of 46 and 18 of 30 countries, respectively, in 2012. By June 2013, more than 2,300 patients had been tested in 23 countries in the WHO European Region with nine laboratory-confirmed MERS-CoV cases. These data indicate that the Region has developed significant capability to detect this emerging virus in accordance with WHO and ECDC guidance. However, not all countries had developed capabilities, and the needs to do so should be addressed. This includes enhancing collaborations between countries to ensure diagnostic capabilities for surveillance of MERS-CoV infections across the European Region.

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.

Genomic characterization of Sebokele virus 1 (SEBV1) reveals a new candidate species among the genus Parechovirus.

We determined the genomic features and the taxonomic classification of Sebokele virus 1 (SEBV1), a previously unclassified arbovirus isolated in 1972 from rodents collected in Botambi, Central African Republic. The complete genome sequence was obtained using a deep sequencing approach (Illumina technology) and dedicated bioinformatics workflows for data analysis. Molecular analysis identified SEBV1 as a picornavirus, most closely related to Ljungan viruses of the genus Parechovirus. The genome has a typical Ljungan virus-like organization, including the presence of two unrelated 2A protein motifs. Phylogenetic analysis confirmed that SEBV1 belongs to the parechovirus phylogroup and was most closely related to the Ljungan virus species. However, it appeared clearly distinct from all members of this phylogroup, suggesting that it represents a novel species of the genus Parechovirus.

Clinical presentation and laboratory findings for the first autochthonous cases of dengue fever in Madeira island, Portugal, October 2012.

An outbreak of dengue fever in Madeira island was reported in 2012. Clinical and laboratory findings of the first two laboratory-confirmed autochthonous cases are reported. Both cases had fever (≥38 °C) and petechial rash. Symptoms also included myalgia, asthenia, nausea, vomiting, anorexia, diffuse abdominal pain, and diarrhoea. The two cases were confirmed by serology and one tested positive for a dengue viral sequence. Dengue virus serotype DEN-1 was identified with probable Central or South American origin.

Laboratory capability for molecular detection and confirmation of novel coronavirus in Europe, November 2012.

A rapid survey by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) Regional Office for Europe ascertained the availability of national reference laboratory testing for a recently detected novel coronavirus as of 28 November 2012. Screening by internal quality controlled upE-RT-PCR assay was available in 23/46 of responding countries in the WHO European Region, of which 19/30 in European Union (EU) and European Economic Area (EEA) countries. Confirmation of positive screened samples by either ORF1b - RT-PCR, or other target RT-PCR assays with sequence analysis or whole-genome sequence analysis was available in 22/46 responding countries of which 18/30 in EU/EEA countries.

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.

Recent expansion of dengue virus serotype 3 in West Africa.

Due to non-existing or limited surveillance in Africa, little is known about the epidemiology of dengue illness in the continent. Serological and virological data obtained from returning European travellers is a key complement to this often flawed information. In the past years, dengue 3 virus has emerged in West Africa and has been detected in travellers returning to Europe. The first dengue epidemic in Cape Verde with more than 17,000 cases from September to December 2009 demonstrated that dengue virus is still expanding worldwide to new territories.

Crimean-Congo hemorrhagic fever in Europe: current situation calls for preparedness.

During the last decade Crimean-Congo hemorrhagic fever (CCHF) emerged and/or re-emerged in several Balkan countries, Turkey, southwestern regions of the Russian Federation, and the Ukraine, with considerable high fatality rates. Reasons for re-emergence of CCHF include climate and anthropogenic factors such as changes in land use, agricultural practices or hunting activities, movement of livestock that may influence host-tick-virus dynamics. In order to be able to design prevention and control measures targeted at the disease, mapping of endemic areas and risk assessment for CCHF in Europe should be completed. Furthermore, areas at risk for further CCHF expansion should be identified and human, vector and animal surveillance be strengthened.

First two autochthonous dengue virus infections in metropolitan France, September 2010.

In September 2010, two cases of autochthonous dengue fever were diagnosed in metropolitan France for the first time. The cases occurring in Nice, southeast France, where Aedes albopictus is established, are evidence of dengue virus circulation in this area. This local transmission of dengue calls for further enhanced surveillance, active case finding and vector control measures to reduce the spread of the virus and the risk of an epidemic.

[Long-term seroprotection against Japanese encephalitis using an inactivated vaccine (Jevax)]. / Séroprotection à long terme avec le vaccin inactivé contre l'encéphalite japonaise (Jevax).

Japanese encephalitis vaccine (Jevax) is an inactivated vaccine using the Nakayama viral strain. Until 2007, Jevax was the only Japanese encephalitis vaccine available in France but the duration of seroprotection after vaccination and exact timing of booster injections was unclear for travelers from non-endemic areas. The purpose of this report is to describe the results of a retrospective study in which neutralizing antibody levels were measured in 71 subjects previously vaccinated with Jevax. All subjects underwent testing at the Pasteur Institute Medical Center as part of preparation for humanitarian missions to endemic Japanese encephalitis areas in 2005-2006. A neutralizing antibody level greater than or equal to 20 was considered as protective. Findings showed that 49 of the 71 subjects (69%) still had protective antibody levels at a median of 4 years after the last Jevax immunization. In multivariate analysis, the only factor correlated with long-term seroprotection was the total number of vaccinations received. Based on these findings, it was concluded that long-term seroprotection after Jevax vaccination requires repeated booster injections even in subjects frequently exposed to the virus. No correlation was found between seroprotection and the interval between the booster injections.

Is there a need for anti-rabies vaccine and immunoglobulins rationing in Europe?

Rabies is a lethal encephalitis caused by a lyssavirus and transmitted from animals to humans via bite wound, scratch wound, or licking of mucous membranes. It is preventable by timely administration of post-exposure prophylaxis (PEP) consisting of four or five doses of rabies vaccine combined, in the most severe cases of exposures, with anti-rabies immunoglobulin (RIG). Although the rabies incidence in humans remains low, rabies is still present in some European countries. Moreover, rabid animals imported from enzootic areas are reported every year in rabies-free areas. These importations threaten the rabies-free status of terrestrial animals in western European countries and challenge the public health surveillance system and the health structures responsible for rabies prophylaxis and control. The importations frequently result in the prescription of a large number of PEP including RIG, especially in western European countries. The situation is inverted in some central and eastern European countries where RIG is underprescribed. Only a limited number of rabies vaccines and particularly of RIG are licensed for use in Europe. Their availability is also limited, a situation that may become worse in the future. It therefore seems important to study the possibility of comparing and unifying national PEP guidelines in Europe, if needed, and to generate effective solutions in the event of a shortage of anti-rabies biological products and RIG in particular, such as rationing these products.

[Tropical arboviral diseases and their implications for Europe: role of the European Centre for Disease Prevention and Control (ECDC)]. / Les arboviroses tropicales et leurs enjeux pour l'Europe: rôle du centre européen pour la prévention et le contrôle des maladies (ECDC).

ropical arboviral diseases are a major public health concern. Recurrent outbreaks of West Nile fever with appearance of different viral strains and the recent 2007 epidemic of Chikungunya in Italy serve as reminders that Europe is not spared by this problem. The European Centre for Disease Prevention and Control (ECDC) is active in evaluating potential arboviruses risks and determining the proper responses. This action is based on the shared knowledge and expertise of the European Union member states. The ECDC works through several networks that it coordinates (laboratory, travel medicine, entomological expertise) and through targeted European research projects.

[Imported cases of dengue fever diagnosed in metropolitan France, from January 2001 to December 2006]. / Dengue d'importation diagnostiquée en France métropolitaine, janvier 2001-décembre 2006.

INTRODUCTION: Dengue fever is the main emerging vector-borne disease worldwide. It was estimated that 40% of the world population is at risk. A potential vector (Aedes albopictus) is present in four French departments of the southeast area of metropolitan France. METHOD: The authors tried to document the number of imported cases of dengue diagnosed from 2001 to 2006, inclusive, as well as their main features. RESULTS: Between 12 and 28 cases of imported dengue were diagnosed every month during that period (eight to 18 cases per month except for years 2001-2002 during which an important dengue epidemic was documented in the French West Indies). Nearly 40% of the cases were imported between June and September during which the vector is active in the metropolitan area. CONCLUSION: This data underlines the strong and close link between the endemic zones of the French territory (French West Indies and Guyana) and the risk of imported cases to metropolitan France. The identification of this "importation track" entails strengthening the system for detecting and managing imported dengue cases in metropolitan France when a dengue epidemic is detected in the French West Indies.

Unknown disease in South Africa identified as arenavirus infection.

On 12 September 2008, a tourist guide organising safari trips, residing in Lusaka, Zambia, was evacuated in a critical condition to Johannesburg, South Africa. She was admitted to a clinic where she died on 14 September about 10 days after the onset of symptoms. The symptoms included a prodromal phase with fever, myalgia, vomiting, diarrhoea, followed by rash, liver dysfunction and convulsions [1]. Cerebral oedema was detected on scan examination. No laboratory specimen was available for investigation.

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.