Clinical trial NCT03010007: Prospective Analysis of Seasonal Influenza - Viral Transmission and Evolution in the City of Basel, Switzerland
Official title: Prospective Analysis of Seasonal Influenza - Viral Transmission and Evolution in the City of Basel, Switzerland [Prospektive Systemanalyse Der Saisonalen Influenza - Virustransmission Und Evolution in Der Stadt Basel] in German
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Influenza
Keywords: Influenza
High-Throughput Nucleotide Sequencing
Viral Transmission
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss Federal Institute of Technology
name: University Children's Hospital Basel
name: University of Basel
First posted: 2017-01-04
Enrollment: 800
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Paediatric or adult patients fulfilling the World Health Organization (WHO) definition of an influenza-like illness. A total number of 1000 influenza PCR-confirmed cases should be included.

Brief summary: Influenza associated illness has a global annual impact with high morbidity and mortality. Transmission mechanisms and rates are under-investigated and overall poorly understood.

This project aims to use epidemiological tools to understand the transmission and evolution of influenza viruses at an individual and population level within a small-scale city (Basel) through a combination of experimental, clinical and mathematical advances. The investigators aim to quantitatively characterize the viral transmission using novel molecular-epidemiological tools based on whole genome sequencing.

Detailed description: In this prospective observational study, paediatric and adult outpatients presenting with influenza-like illness will be enrolled at the emergency departments of the University Hospital Basel (USB), the paediatric University Hospital of both Basel (UKBB), or a network of family doctors (associated with Center of Primary Health Care).

The Clinical Trial Unit at the University Hospital Basel will coordinated the recruitment process, collect data and sample all patients during the influenza season 2016/17. Samples will be collected such as whole blood, serum and DNA, nasopharyngeal swamps to diagnose influenza by polymerase chain reaction (PCR) assay and to determine colonization rates with Staphylococcus aureus and Streptococcus pneumonia. All samples except the first naso-pharyngeal swab for influenza diagnostics will be stored in a biobank and analysed in batches. Each influenza virus isolate will be sequenced using a "whole genome sequencing" approach. The viral transmission and evolution will be analysed using whole genome data for a detailed molecular and phylogenetic tree analysis, respectively. The epidemiological and geographical data will be incorporated into the phylogenetic model.

Specific aims are:

(i) to determine the impact of the most important epidemiological parameters, first focusing on the age profile, followed by children per house hold, and population density, on influenza transmission at an individual and population level, drawing on an analysis of baseline humoral immunity and whole genome sequencing data, (ii) to understand the viral evolution during seasonal epidemics, (iii) to develop dynamic mathematical models that are able to predict viral transmission and evolution based on the retrospective results from (i) and (ii) and to validate this model in future influenza seasons.

To realize the interdisciplinary approach, the investigators will rely on the expertise in mathematical modelling of viral epidemiology and evolution and established geographical expertise, next generation sequencing, clinical epidemiology, and immunologic diagnostic techniques.

Eligibility criteria: Inclusion Criteria:

* Each pediatric or adult patient, which fulfill the Worl Health Organization (WHO) definition of Influenza like illness.
* The case definition includes an acute respiratory infection with coughing, fever ≥38°C, and start of symptoms within the last 10 days.
* Presentation of the patient with influenza-like illness on the emergency ward of the University Hospital Basel or the University Children Hospital of both Basel or a collaborating private practise.
* Patient has to live in the city of Basel.

Exclusion Criteria:

* Patients who are not living in the City of Basel.
* Case definition for influenza like illness is not fulfilled.

Primary outcomes:
measure: Investigation of the phylogenetic relation of viral isolates from participating patients using whole-genome sequencing and bioinformatics
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Federal Institute of Technology Zurich
city: Basel
country: Switzerland
facility: University Children's Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Basel
country: Switzerland
facility: Universitätres Zentrum für Hausarztmedizin beider Basel, University of Basel
Study officials:
affiliation: Clinical Microbiology, University Hospital Basel
name: Adrian Egli, PD Dr. FAMH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Egli A, Saalfrank C, Goldman N, Brunner M, Hollenstein Y, Vogel T, Augustin N, Wuthrich D, Seth-Smith HMB, Roth E, Syedbasha M, Mueller NF, Vogt D, Bauer J, Amar-Sliwa N, Meinel DM, Dubuis O, Naegele M, Tschudin-Sutter S, Buser A, Nickel CH, Zeller A, Ritz N, Battegay M, Stadler T, Schneider-Sliwa R. Identification of influenza urban transmission patterns by geographical, epidemiological and whole genome sequencing data: protocol for an observational study. BMJ Open. 2019 Aug 20;9(8):e030913. doi: 10.1136/bmjopen-2019-030913.