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Progress in Pathogen Genomics as a Prototype for Precision Public Health

Posted on by Muin J. Khoury, Office of Genomics and Precision Public Health, Centers for Disease Control and Prevention, Atlanta, Georgia

four arrows labeled Bacterial Foodborne Illness, Parasitic Diseases, Tuberculosis and Influenza pointing to Pathogen Genomics: A Prototype for Precision Public Health with DNA aroundRapid advances in pathogen genomics have ushered in a new era of “precision public health.” Next-generation sequencing is already enabling more effective investigations of outbreaks of foodborne illnesses, better-targeted tuberculosis control, and more timely and granular influenza surveillance to inform the selection of vaccine strains. In a recent paper in the New England Journal of Medicine, Dr Greg Armstrong, director of the CDC’s Office of Advanced Molecular Detection and coauthors describe how public health agencies have adopted pathogen genomics to improve their effectiveness in almost all domains of infectious disease. This momentum is likely to continue, given the ongoing development in sequencing-related technologies. The following are some examples from the article to highlight the value of pathogen genomics in public health.

Bacterial Foodborne Illness

The national network “PulseNet” for the detection of foodborne outbreaks, which includes more than 80 public health laboratories, has transitioned from pulsed-field gel electrophoresis to whole-genome sequencing. Whole-genome sequencing allows for finer subtyping of pathogens and reveals evolutionary relationships between bacterial isolates, allowing for more rapid outbreak detection and a better understanding of transmission and links between cases. Whole-genome sequencing can also predict phenotypic characteristics, such as virulence, serotype, and antimicrobial resistance.

Tuberculosis

Whole-genome sequencing offers subtyping at much finer resolution than was possible with older technologies and thus more confidence in the inferred relationships among cases. After using whole-genome sequencing selectively for several years, investigators in U.S. tuberculosis control programs have now scaled up the process to sequence isolates from all culture-confirmed cases nationwide.

Influenza

The selection of seasonal influenza vaccine candidate strains is a complex, global undertaking, involving massive surveillance efforts from dozens of countries and contributing organizations. Next-generation sequencing now enables a more efficient “sequence-first” approach, in which original specimens are subjected directly to whole-genome reverse-transcriptase PCR, followed by sequencing. These sequence data provide a highly granular view of viral emergence and allow for a more parsimonious selection of viruses for phenotypic characterization, including antigenic analysis and susceptibility to antiviral agents.

Parasitic Diseases

The parasitic diseases laboratories at CDC are developing a new type of diagnostic test based on the targeted amplification and next-generation sequencing of eukaryotic housekeeping genes. This approach enables the accurate detection of all known potential human parasitic agents present in a blood sample with a single test.

Other Examples

Next-generation sequencing is applicable across the spectrum of important pathogens in public health. For Legionnaires’ disease, for example, finer subtyping has been useful for investigating and responding to outbreaks. For hospital-acquired infections, next-generation sequencing is proving to be an invaluable tool for identifying and investigating outbreaks and also provides a better understanding of transmission at both the hospital and the community level. For human immunodeficiency virus, genetic-sequence data generated for clinical purposes can be analyzed to identify potential clusters for early intervention.

Other applications for next-generation sequencing in public health include insecticide resistance in mosquito vectors of disease, monitoring streptococcal pathogens, and investigating potential clusters of meningitis.

Next steps

Next-generation sequencing is now central to U.S. public health programs for monitoring, controlling, and preventing infectious diseases. Progress is currently needed in several areas, including metagenomics, data integration and data science, and software to facilitate next-generation sequencing workflows. In both academia and public health, pathogen genomics is ushering in a new era in data openness. In the United States, local, state, and federal agencies are uploading data on bacterial foodborne pathogens, influenza, and other pathogens to public databases.

Development of the public health workforce is central to this process. Microbiologists need a strong knowledge base in microbial genomics. Epidemiologists need the skills and tools to translate genomic data into public health action. Both groups need to grasp the basic vocabulary of bioinformatics. Public health should strive to attract professionals with broadly applicable data-science skills. For anyone considering a career in public health, this is an exciting time indeed.

For additional information on CDC activities in pathogen genomics, please consult the Advanced Molecular Detection website. You can also search the CDC Public Health Genomics Knowledge Base for recent information and publications on pathogen genomics in public health, including CDC-authored publications.

Please attend the upcoming CDC Public Health Grand Rounds on January 21, 2020: The Emerging Role of Pathogen Genomics in Public Health.

Posted on by Muin J. Khoury, Office of Genomics and Precision Public Health, Centers for Disease Control and Prevention, Atlanta, GeorgiaTags

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