Whole Genome Sequencing for Surveillance of Diphtheria in Low Incidence Settings

Abstract

Corynebacterium diphtheriae ( C. diphtheriae ) is a relatively rare pathogen in most Western countries. While toxin producing strains can cause pharyngeal diphtheria with potentially fatal outcomes, the more common presentation is wound infections. The diphtheria toxin is encoded on a prophage and can also be carried by Corynebacterium ulcerans and Corynebacterium pseudotuberculosis . Currently, across Europe, infections are mainly diagnosed in travelers and refugees from regions where diphtheria is more endemic, patients from urban areas with poor hygiene, and intravenous drug users. About half of the cases are non-toxin producing isolates. Rapid identification of the bacterial pathogen and toxin production is a critical element of patient and outbreak management. Beside the immediate clinical management of the patient, public health agencies should be informed of toxigenic C. diphtheriae diagnoses as soon as possible. The collection of case-related epidemiological data from the patient is often challenging due to language barriers and social circumstances. However, information on patient contacts, vaccine status and travel/refugee route, where appropriate, is critical, and should be documented. In addition, isolates should be characterized using high resolution typing, in order to identify transmissions and outbreaks. In recent years, whole genome sequencing (WGS) has become the gold standard of high-resolution typing methods, allowing detailed investigations of pathogen transmissions. De-centralized sequencing strategies with redundancy in sequencing capacities, followed by data exchange may be a valuable future option, especially since WGS becomes more available and portable. In this context, the sharing of sequence data, using public available platforms, is essential. A close interaction between microbiology laboratories, treating physicians, refugee centers, social workers, and public health officials is a key element in successful management of suspected outbreaks. Analyzing bacterial isolates at reference centers may further help to provide more specialized microbiological techniques and to standardize information, but this is also more time consuming during an outbreak. Centralized communication strategies between public health agencies and laboratories helps considerably in establishing and coordinating effective surveillance and infection control. We review the current literature on high-resolution typing of C. diphtheriae and share our own experience with the coordination of a Swiss-German outbreak.

Population genomics and antimicrobial resistance in Corynebacterium diphtheriae

“…To this aim, we characterized phenotypically and genotypically a large sample of C. diphtheriae isolates from diverse geographic and temporal origins. We confirmed that the species is made of multiple phylogenetic sublineages [ 9 , 13 , 67 ] and showed that homologous recombination contributes five times more to their diversification than mutation, consistent with previous evidence of recombination in C. diphtheriae populations [ 12 , 13 ].…”

First-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae in Indonesia

“…The other limitation of this study was we did not examine the deoxyribonucleic acid (DNA) sequence of C. diphtheriae to analyze the association between the genetic aspect and the MIC. Genetic information is suggested to be done regularly [62]. Further study may be focused in this issue.…”

Short Communication: Identification and phylogenetic analysis of Corynebacterium diphtheriae isolates from Jakarta, Indonesia based on partial rpoB gene

“…However, we do not have data relating to the patient's travel history. Diphtheria disease will remain a health problem due to the movement of people (Sadoh and Oladokun 2012;Seth-Smith and Egli 2019). Thus, the information on the travel history of infected patients is important to predict the potential transmissions within one country or among countries, so this disease could be prevented in the future.…”