Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response

Frank M. Aarestrup

, Eric W. Brown, Chris Detter, Peter Gerner-Smidt, Matthew W. Gilmour, Dag Harmsen, Rene S. Hendriksen, Roger Hewson, David L. Heymann, Karin Johansson, Kashef Ijaz, Paul S. Keim, Marion Koopmans, Annelies Kroneman, Danilo Lo Fo Wong, Ole Lund, Daniel Palm, Pathom Sawanpanyalert, Jeremy Sobel, and Jørgen Schlundt

Author affiliations: Technical University of Denmark, Lyngby, Denmark (F.M. Aarestrup, R.S. Hendriksen, O. Lund, J. Schlundt); US Food and Drug Administration, College Park, Maryland, USA (E.W. Brown); Los Alamos National Laboratory, Los Alamos, New Mexico, USA (C. Detter); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (P. Gerner-Smidt, K. Ijaz, J. Sobel); Public Health Agency of Canada, Winnipeg, Manitoba, Canada (M.W. Gilmour); University of Münster, Münster, Germany (D. Harmsen); Health Protection Agency, Salisbury, UK (R. Hewson); London School of Hygiene and Tropical Medicine, London, UK (R. Hewson, D. Heymann); Health Protection Agency, London (D. Heymann); European Center for Disease Control and Prevention, Stockholm, Sweden (K. Johansson, D. Palm); Northern Arizona University, Flagstaff, Arizona, USA (P.S. Keim); TGen, Phoenix, Arizona, USA (P.S. Keim); National Institute for Public Health and the Environment, Bilthoven, the Netherlands (M. Koopmans, A. Kroneman); Erasmus MC, Rotterdam, the Netherlands (M. Koopmans, A. Kroneman); World Health Organization, Geneva, Switzerland (D. Lo Fo Wong); and Ministry of Public Health, Nonthaburi, Thailand (P. Sawanpanyalert)

Abstract

The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost. The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories. With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients. Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.

Infectious diseases remain a global challenge. Of the 58 million deaths worldwide each year, 15 million (>25%) are the direct result of infectious diseases (1). This magnitude, while staggering, is an underestimate because it excludes deaths caused by complications from chronic infections that cause end-stage disease (e.g., cirrhosis or malignancy) or by the lingering consequences of a past infection. Moreover, given trends toward globalization of travel and trade (including food), demographic changes (urbanization, aging population), and the increasing effect of human populations on natural environments, infectious disease challenges will continue to emerge, re-emerge, and cause global threats.
A wide range of specialized culturing and subtyping techniques have traditionally been used to confirm the clinical diagnosis and surveillance of infectious diseases. This approach has been used and validated across almost all infectious disease pathogens, including Salmonella enterica, methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, influenza, and enteroviruses. However, the diagnostic basis for the majority of these methods is to sample a single or small number of defining traits for the target pathogen. Owing to technical limitations, such approaches ignore the vast multitude of traits possessed by pathogens that could otherwise be used for a substantially improved understanding of their identity, virulence, and transmission. Furthermore, current diagnostic methods can require several weeks from collecting a biologic sample to full characterization, and this can lead to delays in determining the source and scope of infectious diseases.
In low-income countries, where the time lag is greatest, delays in diagnosis lead to suboptimal treatment, delayed identification of preventable diseases, and, in some instances, exacerbation of outbreaks. Even in countries with sufficient specialized diagnostic capabilities, the current procedures for identification, subtyping, analysis, and information flow are often slow, leading to delays in disease treatment and detection. Delays are often the greatest when dealing with novel pathogens; such delays give the pathogens the opportunity to spread rapidly, as exemplified by the severe acute respiratory syndrome outbreak in 2003, the emergence of influenza A(H1N1) virus in 2009, and the recent outbreak of enterohemorrhagic Escherichia coli in Germany (2–4).