However, this requires highly specific molecular and/or serology-based arbovirus diagnosis, clear and comprehensive registration in medical systems, and funding to allow properly powered studies beyond a single region

However, this requires highly specific molecular and/or serology-based arbovirus diagnosis, clear and comprehensive registration in medical systems, and funding to allow properly powered studies beyond a single region. Overall, most studies scored high on diagnostic specificity (group A, 736/1082, 68%), which is mainly explained by our selection of studies using vaccinees or (partially) molecular or viral-isolation methods to confirm infection of patients of at least one of the study groups that were used for testing cross-reactivity in their study. provides insufficient detail to support conclusions on specificity of serological outcomes with regards to elucidating antibody cross-reactivity. Along with the lack of standardization of assays, metadata such as time of illness onset, vaccination, infection and travel history, age and specificity of serological methods were most frequently missing. Given the critical role of serology for diagnosis and surveillance of arbovirus infections, better standards for reporting, as well as the development of more (standardized) specific serological assays that allow discrimination between exposures to multiple different arboviruses, are a large global unmet need. == Author summary == Arboviruses are notorious for triggering antibodies that may cross-react with (closely) related arboviruses, complicating Obtustatin interpretation of serology-based arbovirus diagnostics and Rabbit Polyclonal to Mst1/2 of epidemiological surveys. This is further complicated by the rapid global spread of arboviruses, that may lead to increasing co-circulation of antigenically related arboviruses, and by the lack of detailed background information on the population tested, methods used and background arbovirus exposures such as prior infections or vaccinations. Here, we aim to provide a better understanding of the complex cross-reactivity patterns as well as the current knowledge and knowledge gaps in differential arbovirus serology. We have done a systematic analysis of reported cross-reactivity patterns from published peer-reviewed articles, using a system that allows assessment of the quality of reported cross-reactivity results. We show that using this approach, the majority of studies lack details needed to reliably assess whether reactivity to antigens from different, related arboviruses is caused by antibody cross-reactivity, or if it reflects antibodies from multiple exposures to these different viruses. Furthermore, there is a strong need for standardization of assays and study designs in future serological studies to compare cross-reactivity results from different studies. Tackling this may lead to improved diagnosis and surveillance of (newly) emerging and/or rapidly spreading arboviruses. == Introduction == In the past two decades, the global impact of arthropod-borne (ARBO) viruses has steadily been increasing due to rapid distribution over larger geographic areas, the emergence of new variants, and new complications arising from the sequel of viral exposures potentially leading to enhanced disease [13]. Major anthropogenic factors contributing to this global spread are increased human travel to or from (sub)tropical arbovirus endemic regions, global transportation of water-retaining objects offering opportunity for dispersal of mosquitos, urbanization and deforestation. Climate change may also have an impact by influencing the geographical and temporal distribution of arthropods and/or reservoir hosts such as migrating birds [37]. Recent examples of unusual arboviral spread are autochthonous chikungunya virus (CHIKV) cases that have been reported in Italy and France throughout the past years [812], Usutu virus (USUV) which is frequently observed in birds and occasionally in humans in Europe [13], the Zika virus (ZIKV) epidemic that rapidly spread to Obtustatin the Pacific islands and the Americas [1420], Crimean Congo Haemorrhagic fever virus (CCHFV) expansion in Europe [6,2123], the first autochthonous West Nile virus (WNV) cases in Germany [24] and the Netherlands [25], and locally acquired dengue virus (DENV) Obtustatin cases in France and Spain [26]. Furthermore, there are indications that other arboviruses such as Mayaro virus (MAYV) are further spreading into the Caribbean and Central and South America, likely causing more outbreaks in the near future [2732]. As clinical symptoms of most arboviruses are very similar and virological (molecular) detection is only possible in a short period after clinical symptoms due to the short arbovirus viremic phase, serology is essential in arboviral diagnosis. However, serology-based differential arbovirus diagnosis is complicated by antibodies induced by a primary arbovirus infection that may cross-react with other closely related arboviruses. This is further complicated by the phenomenon original antigenic sin (OAS), which describes the preferential boosting of these cross-reactive antibodies upon subsequent heterologous arbovirus infections [33]. Together with the current global spread of arboviruses, which increasingly co-circulate [3438],.