Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis

Abstract

Outbreaks of multidrug-resistant bacteria present a frequent threat to vulnerable patient populations in hospitals around the world. Intensive care unit (ICU) patients are particularly susceptible to nosocomial infections due to indwelling devices such as intravascular catheters, drains, and intratracheal tubes for mechanical ventilation. The increased vulnerability of infected ICU patients demonstrates the importance of effective outbreak management protocols to be in place. Understanding the transmission of pathogens via genotyping methods is an important tool for outbreak management. Recently, whole-genome sequencing (WGS) of pathogens has become more accessible and affordable as a tool for genotyping. Analysis of the entire pathogen genome via WGS could provide unprecedented resolution in discriminating even highly related lineages of bacteria and revolutionize outbreak analysis in hospitals. Nevertheless, clinicians have long been hesitant to implement WGS in outbreak analyses due to the expensive and cumbersome nature of early sequencing platforms. Recent improvements in sequencing technologies and analysis tools have rapidly increased the output and analysis speed as well as reduced the overall costs of WGS. In this review, we assess the feasibility of WGS technologies and bioinformatics analysis tools for nosocomial outbreak analyses and provide a comparison to conventional outbreak analysis workflows. Moreover, we review advantages and limitations of sequencing technologies and analysis tools and present a real-world example of the implementation of WGS for antimicrobial resistance analysis. We aimed to provide health care professionals with a guide to WGS outbreak analysis that highlights its benefits for hospitals and assists in the transition from conventional to WGS-based outbreak analysis.

Reliable variant calling during runtime of Illumina sequencing

“…Examples for such time-critical analyses range from the differential diagnosis of genetic disorders in infants 1–4 , to the determination of M . tuberculosis drug resistances 5 , and to the identification of pathogens, virulence factors, drug resistances and paths of disease transmission in infectious disease outbreaks 6,7 . While having considerably higher turnaround times than targeted approaches such as molecular tests, NGS provides a more open view as well as more extensive and reliable results.…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…The introduction of genomic and computational technologies has given new directions in the study of bacterial pathogenesis and vaccine design. 93,94 Plasmodium Plasmodium falciparum undergoes two life cycles: one in humans and the other in mosquitoes. The human host's erythrocytes and hepatocytes usually display modified parasite proteins called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and Plasmodium falciparum hepatocyte membrane protein 1 (PfHMP1), respectively.…”

Communicable Disease Surveillance Ethics in the Age of Big Data and New Technology

“…Recently, it has and is continuing to become faster, less expensive and more informative than other genotypic methods and is being introduced into routine use in public health laboratories (Ashton et al 2016;Satta et al 2017;Inns et al 2017;Gurjav et al 2016). It promises to dramatically improve the accuracy and speed of pathogen identification, antimicrobial resistance (AMR) profiling, biological risk prediction, outbreak identification and pathogen tracking (ECDC 2016;Quainoo et al 2017), with definitive discriminatory power.…”

“…Surveillance and outbreak investigation has always required the use of personal data. The much greater precision of WGS raises new questions of consent and unanticipated harm, but despite its increasing use in public health and hospital laboratories (Quainoo et al 2017;Azarian et al 2015), there has been little discussion of these issues. Unlike public health surveillance, nosocomial outbreak investigations are not protected by legislation and there is no clarity about privacy protection or the need for informed consent when the use of WGS is extended into new domains.…”