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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.

 

Publications

Case numbers of acute hepatitis of unknown aetiology among children in 24 countries up to 18 April 2022 compared to the previous 5 years

Publication date: 12 May 2022

Journal: Eurosurveillance

Authors: Janko van Beek, Pieter L.A. Fraaij, Carlo Giaquinto, Delane Shingadia, Peter Horby, Giuseppe Indolfi, Marion Koopmans

An increase of acute hepatitis of unknown origin has been reported among children in multiple countries. Up to 3 May 2022, 163 cases have been reported from the United Kingdom (UK), of which 11 received a liver transplantation. By 27 April, according to the European Centre for Disease Prevention and Control (ECDC), approximately 55 cases have been reported from 12 other European countries, 12 cases from the United States, 12 from Israel, and 1 from Japan. The cause of this possible outbreak is unclear, but based on initial assessment, an infectious aetiology is considered. Together, a group of European clinical trial networks and the paediatric gastroenterology–hepatology and infectious diseases societies set up a rapid online survey among members to assess the extent and geographical distribution of the suspected outbreak from 1 January until 18 April 2022 in comparison to the incidence in the previous 5 years.