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Open Access Highly Accessed Research article

Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source

Fernando González-Candelas12*, María Alma Bracho12, Borys Wróbel134 and Andrés Moya12

Author Affiliations

1 Joint Research Unit ‘Genómica y Salud’ CSISP (FISABIO), Instituto Cavanilles/Universidad de Valencia, c/ Catedrático José Beltrán, 2 46980-Paterna, Valencia, Spain

2 Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Valencia, Spain

3 Department of Genetics and Marine Biotechnology, Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55, 81-712 Sopot, Poland

4 Laboratory of Bioinformatics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznań, Umultowska 89, 61-614 Poznań, Poland

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BMC Biology 2013, 11:76  doi:10.1186/1741-7007-11-76

Published: 19 July 2013

Abstract

Background

Molecular phylogenetic analyses are used increasingly in the epidemiological investigation of outbreaks and transmission cases involving rapidly evolving RNA viruses. Here, we present the results of such an analysis that contributed to the conviction of an anesthetist as being responsible for the infection of 275 of his patients with hepatitis C virus.

Results

We obtained sequences of the NS5B and E1-E2 regions in the viral genome for 322 patients suspected to have been infected by the doctor, and for 44 local, unrelated controls. The analysis of 4,184 cloned sequences of the E1-E2 region allowed us to exclude 47 patients from the outbreak. A subset of patients had known dates of infection. We used these data to calibrate a relaxed molecular clock and to determine a rough estimate of the time of infection for each patient. A similar analysis led to an estimate for the time of infection of the source. The date turned out to be 10 years before the detection of the outbreak. The number of patients infected was small at first, but it increased substantially in the months before the detection of the outbreak.

Conclusions

We have developed a procedure to integrate molecular phylogenetic reconstructions of rapidly evolving viral populations into a forensic setting adequate for molecular epidemiological analysis of outbreaks and transmission events. We applied this procedure to a large outbreak of hepatitis C virus caused by a single source and the results obtained played a key role in the trial that led to the conviction of the suspected source.

Keywords:
HCV; Outbreak; Forensics; Molecular epidemiology; Nosocomial transmission; Compartmentalization; Maximum likelihood; Dating transmission events; Viral evolution