Clinical and molecular study of Corynebacterium diphtheriae systemic infections in France. Coryne Study Group

Abstract

Diphtheria is a disease with a long history that almost completely disappeared from developed countries. In addition, until 1987, systemic infections involving Corynebacterium diphtheriae were rare. However, in 1990, an epidemic occurred in Russia. These two circumstances have provided the stimulus to gain insight into the situation in France. In fact, between 1987 and 1993, a total of 59 C. diphtheriae strains were isolated. Epidemiological data were collected for patients from whom 40 strains were isolated from normally sterile sites, including 34 from blood cultures, and half of the bacteremic patients developed endocarditis. Osteoarticular involvement was noted in 11 of these 40 patients, including 5 bacteremic patients. The fatality rate following bacteremia was 36%, despite specific antibiotic treatment (beta-lactams and aminoglycosides). The mean age of the participants was 38 years, with half of the patients subsisting under low socioeconomic conditions and suffering from homelessness or alcoholism. Apparently, the skin turned out to be the major route of transmission in this reemerging disease. Eighty-eight percent of the isolates belonged to the C. diphtheriae biotype mitis. These were found predominantly in the Paris area, and most were of the same ribotype. Those isolates originating from the overseas territories (Guyana and New Caledonia) belonged to C. diphtheriae biotype gravis. No strains were positive for the tox gene by PCR. This study attests to the persistent circulation in France of C. diphtheriae in the form of systemic infections. The matter is especially significant since these strains are nontoxigenic and are of a unique ribotype. The strains are, however, sensitive to most antibiotics, although 20% are rifampin resistant.

Microbiological changes and diversity in autochthonous non-toxigenic Corynebacterium diphtheriae isolated in France

“…In England and Wales, the number of non‐toxigenic isolates increased between 1986 (four isolates) and 2006 (68 isolates), peaking at 294 isolates in 2000 (http://www.hpa.org.uk/). Other countries with vaccination programmes have reported similar observations . Clinical features of the infections due to non‐toxigenic isolates may be indistinguishable from those due to toxigenic isolates, such as cutaneous infections and pharyngitis.…”

“…These isolates, consecutively collected throughout mainland France between 1977 and 2011, were either sent by clinical laboratories for confirmation of identification and toxigenic assessment, or provided by the Institut Pasteur Collection. Twenty‐four of these isolates have previously been characterized .…”

“…Clinical features of the infections due to non‐toxigenic isolates may be indistinguishable from those due to toxigenic isolates, such as cutaneous infections and pharyngitis. Moreover, they have been associated with invasive infections such as bacteraemia, endocarditis, and bone and joint infections .…”

Intracellular viability of toxigenic Corynebacterium diphtheriae strains in HEp-2 cells

“…diphtheriae infections are associated with a range of clinical outcomes from asymptomatic carriage to fatal respiratory diphtheria or invasive disease. Disease vs asymptomatic colonisation is believed to depend both on host factors and on genetic di¡erences among C. diphtheriae strains [1,9]. Diphtheria bacilli are generally considered an extracellular coloniser.…”

“…The systemic infections caused by C. diphtheriae [9,10] suggest that the organism is not only able to adhere to host epithelial cells of respiratory mucosa but is also able to penetrate and gain access to deeper tissues. Additional studies using cultured cell lines are necessary in order to investigate the role of invasion in the pathogenesis of diphtheria bacilli and provide insight into the mechanisms involved.…”