Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

Abstract

bHuman infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by Corynebacterium ulcerans, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by Corynebacterium diphtheriae strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight C. diphtheriae cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a C. diphtheriae infection and one due to C. ulcerans. MLST demonstrated that the majority (87.5%; 7/8) of C. diphtheriae strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in C. ulcerans were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to C. diphtheriae. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required.

Toxigenic Corynebacterium ulcerans isolated from a hunting dog and its diphtheria toxin antibody titer

“…The MLST method used in the present study employed the nucleotide sequencing of housekeeping genes commonly utilized for C. diphtheriae MLST , as well as in recent MLST analyses of C. ulcerans . Although we selected different nucleotide regions for identifying alleles than those used in other studies, our method had sufficient power and resolution to type 24 distinct C. ulcerans strains and isolates.…”

“…Whether Group II organisms, which our findings indicate may be limited to wild or near-wild animals, can spread to humans remains unknown; however, this information could prove pivotal in elucidating the origin of the human C. ulcerans infections that have continued to emerge in developed countries. The MLST method used in the present study employed the nucleotide sequencing of housekeeping genes commonly utilized for C. diphtheriae MLST (30), as well as in recent MLST analyses of C. ulcerans (36,37). Although we selected different nucleotide regions for identifying alleles than those used in other studies, our method had sufficient power and resolution to type 24 distinct C. ulcerans strains and isolates.…”

The killing of macrophages byCorynebacterium ulcerans

“…25 Furthermore, by acquisition of new genes, this repertoire can change quickly, 8 supporting the necessity of a constant surveillance of this pathogen. 44 The contribution of putative virulence proteins identified so far and of other components of the cell, like glycolipids, which play an important role in virulence of C. diphtheriae, M. tuberculosis or R. equi, 38,39,45,46 has to be elucidated at the molecular level by genetic experiments with defined mutants in future.…”

Colonization of human epithelial cell lines by Corynebacterium ulcerans from human and animal sources

“…Furthermore, by acquisition of new genes, this repertoire can change quickly (Meinel et al, 2014), supporting the necessity of constant surveillance of this pathogen (Both et al, 2015). The contribution of putative virulence proteins identified so far and of other components of the cell, like glycolipids, which play an important role in virulence of C. diphtheriae, Mycobacterium tuberculosis and Rhodococcus equi (Indrigo et al, 2003;Axelrod et al, 2008;Moreira et al, 2008;Sydor et al, 2013), has to be elucidated in the future at the molecular level by genetic experiments with defined mutants.…”