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Now Watch This: Genomic Epidemiology

Categories: epidemiology, genomics, whole genome sequence

Staphylococcus aureus bacteria

Staphylococcus aureus bacteria

Late last year, Science magazine published a list of six Areas to Watch in 2012. Number 6 on the list, NASA’s Curiosity rover, recently touched down on Mars. The Higgs boson (#1) has been found, faster-than-light neutrinos (#2) have been debunked, and further developments on stem-cell metabolism (#3) and treatments for intellectual disability (#5) are in progress.  

Now genomic epidemiology (#4) is approaching the public health launch pad. As Science’s editors predicted, pathogen genome sequences are being used to “determine quickly where newly emerging diseases come from, whether microbes are resistant to antibiotics, and how they are moving through a population.”    

This summer, two studies described the use of high-throughput whole genome sequencing (WGS) to investigate transmission of drug-resistant bacteria among hospitalized patients (Köser 2012a, Snitkin 2012). 

These follow reports published last year of WGS applied to investigations of the massive foodborne outbreak of Shiga toxin-producing Escherichia coli O104:H4 in Europe, the 2010 cholera outbreak in Haiti, and a 2006-2008 outbreak of tuberculosis in Canada.       

Falling cost and turnaround time could help transform WGS from a retrospective research technique into a tool for clinical microbiologists and public health investigators. Two timely articles (Köser 2012b, Loman 2012) outline what more is needed for WGS to become effective and practical for routine use. The key considerations fall into two main categories: choosing the right applications and developing appropriate infrastructure.   

WGS will be most useful when it leads to earlier, more informed, and more cost-effective decision-making. Köser et al. suggest that: 

The most compelling immediate applications for WGS are molecular epidemiology for the purposes of surveillance and outbreak investigation (e.g. for MRSA) and drug susceptibility testing for organisms that are either slow growers or difficult to culture (e.g. MTBC and HIV). 

Bacterial genotyping techniques commonly used in outbreak investigations have limited power of resolution because they target only small bits of the genome. For example, although pulsed-field gel electrophoresis (PFGE) quickly identified outbreak-associated cholera isolates in Haiti, phylogenetic analysis based on WGS was required to distinguish among possible sources of the outbreak strain. Targeted genotyping is also in use for drug susceptibility testing in certain public health settings. For example, US government guidelines already recommend genotypic HIV drug-resistance testing for all persons with HIV infection when they enter into care. WGS could be used to detect minor variants in mixed viral populations and help clinicians recognize anti-retroviral drug resistance that evolves during treatment. 

Clinical translation of human WGS data is currently limited by the number of “clinically actionable” variants. In contrast, translating pathogen WGS for public health hinges on developing appropriate laboratory and bioinformatics infrastructure. Important decisions include where and how to perform WGS, how to conduct quality assurance, and how to analyze and share data in a way that supports informed and timely public health action. As Köser et al. correctly point out, a continuously updated and annotated database of pathogen genomes is crucial. 

Following the successful use of PFGE in a large outbreak in 1993, CDC and the Association of Public Health Laboratories (APHL) developed PulseNet to assist epidemiologists investigating foodborne outbreaks. PulseNet is a national network that supports a continuously updated database, as well as a communication channel for rapid communication among public health and food regulatory agency laboratories. The 16th Annual PulseNet Update Meeting just held in Atlanta included presentations on WGS and data management issues in genomic molecular surveillance.

Previous OPHG blog posts: E. Coli Sprouts in Germany and No Genome is an Island.

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