Status and potential of bacterial genomics for public health practice: a scoping review

Abstract

Background: Next-generation sequencing (NGS) is increasingly being translated into routine public health practice, affecting the surveillance and control of many pathogens. The purpose of this scoping review is to identify and characterize the recent literature concerning the application of bacterial pathogen genomics for public health practice and to assess the added value, challenges, and needs related to its implementation from an epidemiologist's perspective.

Methods: In this scoping review, a systematic PubMed search with forward and backward snowballing was performed to identify manuscripts in English published between January 2015 and September 2018. Included studies had to describe the application of NGS on bacterial isolates within a public health setting. The studied pathogen, year of publication, country, number of isolates, sampling fraction, setting, public health application, study aim, level of implementation, time orientation of the NGS analyses, and key findings were extracted from each study. Due to a large heterogeneity of settings, applications, pathogens, and study measurements, a descriptive narrative synthesis of the eligible studies was performed.

Results: Out of the 275 included articles, 164 were outbreak investigations, 70 focused on strategy-oriented surveillance, and 41 on control-oriented surveillance. Main applications included the use of whole-genome sequencing (WGS) data for (1) source tracing, (2) early outbreak detection, (3) unraveling transmission dynamics, (4) monitoring drug resistance, (5) detecting cross-border transmission events, (6) identifying the emergence of strains with enhanced virulence or zoonotic potential, and (7) assessing the impact of prevention and control programs. The superior resolution over conventional typing methods to infer transmission routes was reported as an added value, as well as the ability to simultaneously characterize the resistome and virulome of the studied pathogen. However, the full potential of pathogen genomics can only be reached through its integration with high-quality contextual data.

Conclusions: For several pathogens, it is time for a shift from proof-of-concept studies to routine use of WGS during outbreak investigations and surveillance activities. However, some implementation challenges from the epidemiologist's perspective remain, such as data integration, quality of contextual data, sampling strategies, and meaningful interpretations. Interdisciplinary, inter-sectoral, and international collaborations are key for an appropriate genomics-informed surveillance.

Keywords: Bacterial infections; Epidemiology; Genomics; Next-generation sequencing; Public health practice; Scoping review; Whole-genome sequencing.

Fig. 1

Focus of the scoping review on pathogen genomics for public health practice. Different domains in the field of infectious diseases require access to the same pathogen genomic data. Whole-genome sequencing (WGS) has the ability to inform and improve individual patient care, by identifying the species, determining its pathogenic potential, and testing its susceptibility to antimicrobial drugs. WGS also provides data for public health surveillance about the relatedness of the pathogen to other strains to investigate transmission routes, monitor trends over time, and allow the identification and control of outbreaks and new threats. Research is a knowledge driver providing reference data, methods, and a deeper understanding about the underlying biological mechanisms to the other domains. The focus of this scoping review is on the use of WGS as a public health tool, i.e., at the level of the population

Fig. 2

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram

Fig. 3

Integration of multiple data types. The anticipated workflow of infection prevention and control includes the following: (1) samples are obtained from cases infected with a certain pathogen, as well as from other sources such as the environment, food, and/or animals following the One Health approach; (2) pathogens are isolated, and information concerning the biological characteristics is obtained through classical microbiological testing. Phenotypic tests are still required to feed databases and confirm genotype-phenotype associations. Culturing steps (isolation) are often preceding genome sequencing; however, sequencing directly from clinical samples is also possible using culture-independent methods (metagenomics); (3) high-throughput sequence data is generated (other -omics technologies such as transcriptomics, proteomics, and metabolomics can complement the genomic information); (4) relationships among isolates and specific characteristics are inferred based on sequence information obtained through bioinformatics tools; (5) to come to a meaningful outcome (i.e., transmission chains, cluster identification, source tracing, key phenotypic attributes), the genomic evidence is combined with epidemiological metadata (time, place, exposures, etc.) from field epidemiological investigations, clinical data obtained through the healthcare system, biological characteristics obtained through classic microbiological methods, and big data on natural and social factors. Finally, infection prevention and control measures can be conducted on the basis of this aggregated information