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POS-ER-Disease X: Perpetual Observational Study among patients with unexplained febrile illness

High-density urban areas are increasingly becoming the hubs for the explosive spread of infectious disease outbreaks. Drivers for disease emergence include demographic change, climate change, globalization of travel and trade, and societal and political unrest. Recent widespread outbreaks of Ebola, dengue, Zika, and COVID-19 are prime examples, and more outbreaks are predicted to occur, although the exact locations and trajectories remain unclear. Europe is at risk: over the past decade, the geographic range of tickborne encephalitis and West Nile virus infection has widened, local cases of transmission and an outbreak of dengue virus have been observed, and incursions of invasive mosquitos has expanded from areas around the Mediterranean northward. Large-scale outbreaks of Usutu viruses in northern European birds and infection of blood donors illustrate that Northern Europe may also be at risk.

The rapid incursion and spread of SARS-CoV-2 have illustrated the vulnerability of clinical centers as they have become hubs for further amplification due to the lack of preparedness. Therefore, this study will focus on preparing for a ‘Disease X ‘ scenario, defined as an unexplained febrile illness with unusual epidemiology and/or clinical presentation and of likely virus etiology.

We focus on specialized infectious disease hospitals in high-density urban areas as sentinel sites for the development and deployment of an observational study using a generic clinical characterization protocol (CCP) for emerging infections. Cities are selected strategically to include regions at greatest risk for arboviral emergence, emergence of outbreaks in socially vulnerable refugee populations, or introductions through international travel and trade.

The primary objectives of this study are:

  • To prepare a clinical network for outbreak response;
  • To describe the patient population enrolled in the POS;
  • To describe variations in current practices in diagnosing and treating patients with severe unexplained syndrome meeting the case definitions in the CCP;
  • To identify possible barriers to deployment of the CCP with research sampling in clinical settings;
  • To describe treatments of these patients;
  • To continuously evaluate best practices related to patient enrolment and data collection to improve study execution.

Secondary objectives of this study are:

  • To test the application of metagenomic sequencing for resolving syndromes of unknown etiology;
  • To assess the possible role of arboviruses and other rare EID in unexplained illness.