Risk factors associated with sustained circulation of six zoonotic arboviruses: a systematic review for selection of surveillance sites in non-endemic areas

Arboviruses represent a signifcant burden to public health and local economies due to their ability to cause unpredictable and widespread epidemics. To maximize early detection of arbovirus emergence in non-endemic areas, surveillance eforts should target areas where circulation is most likely. However, identifying such hotspots of potential emergence is a major challenge. The ecological conditions leading to arbovirus outbreaks are shaped by complex interactions between the virus, its vertebrate hosts, arthropod vector, and abiotic environment that are often poorly understood. Here, we systematically review the ecological risk factors associated with the circulation of six arboviruses that are of considerable concern to northwestern Europe. These include three mosquito-borne viruses (Japanese encephalitis virus, West Nile virus, Rift Valley fever virus) and three tick-borne viruses (Crimean-Congo hemorrhagic fever virus, tick-borne encephalitis virus, and louping-ill virus). We consider both intrinsic (e.g. vector and reservoir host competence) and extrinsic (e.g. temperature, precipitation, host densities, land use) risk factors, identify current knowledge gaps, and discuss future directions. Our systematic review provides baseline information for the identifcation of regions and habitats that have suitable ecological conditions for endemic circulation, and therefore may be used to target early warning surveillance programs aimed at detecting multi-virus and/or arbovirus emergence

Toscana, West Nile, Usutu and tick-borne encephalitis viruses : external quality assessment for molecular detection of emerging neurotropic viruses in Europe, 2017

Background: Neurotropic arboviruses are increasingly recognised as causative agents of neurological disease in Europe but underdiagnosis is still suspected. Capability for accurate diagnosis is a prerequisite for adequate clinical and public health response. Aim: To improve diagnostic capability in EVD-LabNet laboratories, we organised an external quality assessment (EQA) focusing on molecular detection of Toscana (TOSV), Usutu (USUV), West Nile (WNV) and tick-borne encephalitis viruses (TBEV). Methods: Sixty-nine laboratories were invited. The EQA panel included two WNV RNA- positive samples (lineages 1 and 2), two TOSV RNA- positive samples (lineages A and B), one TBEV RNA- positive sample (Western subtype), one USUV RNA- positive sample and four negative samples. The EQA focused on overall capability rather than sensitivity of the used techniques. Only detection of one, clinically relevant, concentration per virus species and lineage was assessed. Results: The final EQA analysis included 51 laboratories from 35 countries; 44 of these laboratories were from 28 of 31 countries in the European Union/European Economic Area (EU/EEA). USUV diagnostic capability was lowest (28 laboratories in 18 countries), WNV detection capacity was highest (48 laboratories in 32 countries). Twenty-five laboratories were able to test the whole EQA panel, of which only 11 provided completely correct results. The highest scores were observed for WNV and TOSV (92%), followed by TBEV (86%) and USUV (75%). Conclusion: We observed wide variety in extraction methods and RT- PCR tests, showing a profound absence of standardisation across European laboratories. Overall, the results were not satisfactory; capacity and capability need to be improved in 40 laboratories

Variable sensitivity in molecular detection of Zika virus in European expert laboratories : external quality assessment, november 2016

Zika virus (ZIKV) infections are a significant public health concern. A strong capability for ZIKV detection is an absolute requirement for adequate preparedness and response strategies and individual patient care. The objective of this study was to assess and improve the capability of European expert laboratories for molecular testing for ZIKV through an external quality assessment (EQA) scheme. Laboratories were provided a panel of 12 samples which included negative samples, samples containing African-or Asian-lineage ZIKV at various concentrations (10(3) to 10(9) copies/ml), and samples containing dengue virus, yellow fever virus, or chikungunya virus. The results were analyzed on the basis of the outcomes of testing for the samples and the extraction and detection method used. Samples with a ZIKV RNA status scored correctly by >50% of the laboratories were designated the core sample. A total of 85 panel outcomes were submitted by 50 laboratories in 31 countries. The results designated all samples as core samples. Thirty-three percent (28/85) of the panel outcomes identified all samples. Analysis at the laboratory level showed that only 40% of the laboratories (20/50), representing 45% of the countries, scored sufficiently; i.e., they had at least one test operational that scored all core samples correctly. There is a need for improvement of the molecular detection of ZIKV in 60% of the participating laboratories. While the specificity of the tests was more robust, the results of the EQA showed large variation in test sensitivity. Improvements should focus on both nucleic acid extraction and ZIKV detection methods

External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021

Background: Countries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS- CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration. Aim: The aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment ( EQA) based on proficiency testing. Methods: The EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS- CoV-2 serological standards were sent to 56 laboratories in 30 countries. Results: The overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS- CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards. Conclusion: Our EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti SARS- CoV-2 antibodies are available.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021

Background: Countries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS- CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration. Aim: The aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment ( EQA) based on proficiency testing. Methods: The EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS- CoV-2 serological standards were sent to 56 laboratories in 30 countries. Results: The overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS- CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards. Conclusion: Our EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti SARS- CoV-2 antibodies are available