Outbreak of Corynebacterium diphtheriae among asylum seekers in Belgium in 2022: operational challenges and lessons learnt.

Since 2022, European countries have been facing an outbreak of mainly cutaneous diphtheria caused by toxigenic Corynebacterium diphtheriae among asylum seekers. In Belgium, between 1 March and 31 December 2022, 25 cases of toxigenic C. diphtheriae infection were confirmed among asylum seekers, mostly among young males from Afghanistan. Multi-locus sequence typing showed that most isolates belonged to sequence types 574 or 377, similar to the majority of cases in other European countries. The investigation and management of the outbreak, with many asylum seekers without shelter, required adjustments to case finding, contact tracing and treatment procedures. A test-and-treat centre was organised by non-governmental organisations, the duration of the antimicrobial treatment was shortened to increase compliance, and isolation and contact tracing of cases was not possible. A vaccination centre was opened, and mobile vaccination campaigns were organised to vaccinate a maximum of asylum seekers. No more cases were detected between end December 2022 and May 2023. Unfortunately, though, three cases of respiratory diphtheria, including one death, were reported at the end of June 2023. To prevent future outbreaks, specific attention and sufficient resources should be allocated to this vulnerable population, in Belgium and at international level.

Multidrug-resistant Corynebacterium diphtheriae in people with travel history from West Africa to France, March to September 2023.

We describe 10 unlinked cases of Corynebacterium diphtheriae infection (nine cutaneous, one respiratory) in France in 2023 in persons travelling from Guinea, Mali, Senegal, Niger or Nigeria and Central African Republic. Four isolates were toxigenic. Seven genomically unrelated isolates were multidrug-resistant, including a toxigenic respiratory isolate with high-level resistance to macrolides and beta-lactams. The high rates of resistance, including against first-line agents, call for further microbiological investigations to guide clinical management and public health response in ongoing West African outbreaks.

Clinical Characteristics of Corynebacterium ulcerans Infection, Japan.

Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001-2020. During 2010-2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.

Evaluation and validation of a commercial ELISA versus the in vitro toxin neutralization assay for determination of diphtheria anti-toxin in human serum.

Introduction. Diphtheria is a potentially life-threatening infection and remains endemic in many low- and middle-income countries (LMICs). A reliable, low-cost method for serosurveys in LMICs is warranted to estimate the accurate population immunity to control diphtheria.Hypothesis/Gap Statement. The correlation between the ELISA results against diphtheria toxoid and the gold standard diphtheria toxin neutralization test (TNT) values is poor when ELISA values are <0.1 IU ml-1, which results in inaccurate estimates of susceptibility in populations when ELISA is used for measuring antibody levels.Aim. To explore methods to accurately predict population immunity and TNT-derived anti-toxin titres from ELISA anti-toxoid results.Methodology. A total of 96 paired serum and dried blood spot (DBS) samples collected in Vietnam were used for comparison of TNT and ELISA. The diagnostic accuracy of ELISA measurement with reference to TNT was assessed by area under the receiver operating characteristic (ROC) curve (AUC) and other parameters. Optimal ELISA cut-off values corresponding to TNT cut-off values of 0.01 and 0.1 IU ml-1 were identified by ROC analysis. A method based on the multiple imputation approach was also applied to estimate TNT measurements in a dataset that only included ELISA results. These two approaches were then applied to ELISA results previously generated from 510 subjects in a serosurvey in Vietnam.Results. The ELISA results on DBS samples showed a good diagnostic performance compared to TNT. The cut-off values for ELISA measurement corresponding to the TNT cut-off values of 0.01 IU ml-1 were 0.060 IU ml-1 in serum samples, and 0.044 IU ml-1 in DBS samples. When a cut-off value of 0.06 IU ml-1 was applied to the 510 subject serosurvey data, 54 % of the population were considered susceptible (<0.01 IU ml-1). The multiple imputation-based approach estimated that 35 % of the population were susceptible. These proportions were much larger than the susceptible proportion estimated by the original ELISA measurements.Conclusion. Testing a subset of sera by TNT combined with ROC analysis or a multiple imputation approach helps to adjust ELISA thresholds or values to assess population susceptibility more accurately. DBS is an effective low-cost alternative to serum for future serological studies for diphtheria.

Clinico-Epidemiological Profile and Predictors of Poor Outcome Among Children During a Diphtheria Outbreak in Haryana.

OBJECTIVE: To study the clinico-epidemiological profile and predictors of poor outcome in an outbreak of diphtheria. OUTCOME: Records of 390 children admitted with the diagnosis of clinical diphtheria in a tertiary care teaching hospital in Nuh, Haryana, from January, 2018 to December, 2020 were analysed with respect to demographic details, immunization status, clinical features, complications and mortality. Patients were divided into survivors and non-survivors, and various variables were compared between the two groups to identify the factors associated with poor outcome. RESULTS: Out of 390 cases, data of 318 (81.5%) was included. Young children (median age 5 year) were predominantly affected, and only 8 (2.5%) children were fully immunized. Pseudomembrane was present in 245 (77%) cases. Albert staining and culture were positive in 84.6% (269) and 12.9% (41) cases, respectively. Complications developed in 48.4% (n=154) cases and included: airway compromise 22.6% (n=72), diphtheritic cardiomyopathy 12.9% (n=41), acute kidney injury 3.7% (n=12), thrombocytopenia 8.5% (n=27) and hepatitis 0.6% (n=2) cases. Anti-diphtheritic serum (ADS) was administered to all admitted patients. Tracheostomy was done in (n=57) (17.9%) children. Case fatality rate was 17.9%. CONCLUSION: Diphtheria mostly affected young unvaccinated or partially vaccinated children. Mortality was high in unimmunized or partially immunized young children and those with bull neck, pseudomembrane, delayed (≥5 days) administration of ADS, acute kidney injury, thrombocytopenia and leukocytosis. Myocarditis was strongly associated with high mortality.

A case of fulminant respiratory diphtheria in a 24-year-old Afghan refugee in Austria in May 2022: a case report.

PURPOSE: Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration. METHODS: Report of a case of fulminant, imported respiratory diphtheria in an otherwise healthy 24-year-old Afghan refugee in Austria in May 2022. RESULT: This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death. CONCLUSION: In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised.

Outbreak of imported diphtheria with Corynebacterium diphtheriae among migrants arriving in Germany, 2022.

From July 2022, cases of imported diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany. Up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory-confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n = 17). Phylogeny and available journey information indicate that most cases (n = 19) were infected along the Balkan route. Active case finding, increased laboratory preparedness and epicentre localisation in countries along this route are important.

Detection of diphtheria toxin production by toxigenic corynebacteria using an optimized Elek test.

PURPOSE: Diphtheria, still present in many countries of the world, is caused by toxigenic strains of species of the Corynebacterium diphtheriae complex, mainly Corynebacterium diphtheriae and the emerging zoonotic pathogen C. ulcerans. The immunoprecipitation test according to Elek is the gold standard for detection of the major virulence factor diphtheria toxin (DT) in toxigenic corynebacteria. Due to its sophisticated methodological requirements, the classical Elek test is performed mainly by specialized reference laboratories. It was revealed that the current modification of the Elek test does not detect the toxin in weakly toxigenic isolates. Therefore, a more robust method for detecting free DT is urgently needed, especially for toxigenic C. ulcerans strains which are known to produce often much lower amounts of DT than C. diphtheriae. METHODS: Thirty-one tox-positive C. ulcerans isolates with a negative standard Elek test result previously determined as NTTB (non-toxigenic tox bearing) were re-analyzed in this study using a modified immunoprecipitation method optimized regarding different parameters including type and concentration of antitoxin, medium volume, inoculum distance from the antitoxin disk and position of controls. RESULTS: All 31 C. ulcerans strains tested positive in the optimized Elek test. CONCLUSION: Only with a reliable and easy-to-handle method for detecting the toxigenicity of C. ulcerans, it is possible to assess the etiological role of this emerging zoonotic bacterium in human pathology.

[Analysis on identification and traceability of one non-toxigenic Corynebacterium diphtheriae from a patient with diabetic foot in Hainan province].

There is a rare case of an elderly diabetic with diabetic foot infection at Hainan General Hospital in September 2021, which was diagnosed as Corynebacterium diphtheriae infection incidentally on routine culture with conventional methods and molecular biological approaches, to aid in diagnosis in clinical practice. Owing to smear staining, Albert staining and VITEK 2 system, automated identification systems viz matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) confirmed combing with 16S ribosomal RNA (16S rRNA) gene has been used for the taxonomic classification of bacteria. Otherwise, toxin gene tox was done for diphtheria toxin synthesis. The isolate was Gram-stain-positive, rod-like arrangement with irregular thickness, with characteristic metachromatic granules, ferment most sugars and homology of 16S rRNA analyses with C. diphtheriae NCTC11397T (MW682323.1) was greater than a 100% possibility, toxin gene tox was negative. The findings lay the foundation to clinical identify and trace of non-toxigenic C. diphtheriae. Moreover, this work provides insights into the non-toxigenic C.diphtheriae that contribute to recognized risk of non-toxigenic C.diphtheriae infections.

Case Report: Bloodstream Infection with Toxigenic Corynebacterium diphtheriae and Gram-Negative Sepsis in a Child with Burns.

Corynebacterium (C.) diphtheriae is the agent for a contagious infection, diphtheria. It may manifest as pharyngitis with pseudomembrane formation and cervical lymphadenopathy, cutaneous infection, or as an asymptomatic carrier. Corynebacterium (C.) diphtheriae is not an invasive organism and it remains in the superficial layers of skin lesions and respiratory mucosa. Systemic complications, such as bacteremia, are rare. We report a case of toxigenic C. diphtheriae detected from blood culture of a 1-year-old male patient with burns, who succumbed to the infection after 8 days of stay in the hospital. Patient did not have specific clinical features suggestive of diphtheria. Initial identification of C. diphtheriae was done based on culture, Albert stain findings, biochemical tests and subsequently toxigenicity testing was done by polymerase chain reaction. Although diphtheria vaccination in infancy is universally recommended since the creation of the Expanded Program on Immunization in the 1970s, there have been reports of toxigenic strains of C. diphtheriae in a considerable number of cases. Rapid and accurate identification of C. diphtheriae infection is crucial to prevent mortality. Continued surveillance for diphtheria is needed to reduce transmission and mortality rates.

Toxigenic Corynebacterium diphtheriae Infection in Cat, Texas, USA.

We report a toxigenic strain of Corynebacterium diphtheriae isolated from an oozing dermal wound in a pet cat in Texas, USA. We also describe the epidemiologic public health efforts conducted to identify potential sources of infection and mitigate its spread and the molecular and genetic studies performed to identify the bacterium.

A diphtheria outbreak in Johor Bahru, Malaysia: Public health investigation and response.

INTRODUCTION: Diphtheria is an acute infectious disease caused by Corynebacterium diphtheriae. Although the incidence of diphtheria worldwide has rapidly declined following the largely successful diphtheria toxoid-based vaccines, concerns persist for those who were unvaccinated or incompletely vaccinated. In this report, we describe a recent diphtheria outbreak in Malaysia involving four confirmed diphtheria cases. METHODOLOGY: The outbreak investigation efforts and epidemiological characteristics of a diphtheria outbreak in Malaysia are described. For all suspected cases, swabs were taken and sent for isolation of Corynebacterium diphtheriae and confirmation of toxigenic strains. RESULTS: The index case was a two-year-old child living with his family in a welfare home. Following contact tracing efforts and investigation for suspected cases, seven samples came back as culture positive for Corynebacterium diphtheriae. Confirmation of toxigenic strains was performed using PCR and Elek's test, which showed 100% correlation in positivity for four of the samples. All four confirmed cases were below 18 years of age, and three of them did not have complete vaccination history (two unvaccinated, one unknown). The index case eventually succumbed due to severe diphtheria with multiorgan failure while all the other cases were discharged healthy. CONCLUSIONS: In Malaysia, despite good vaccination coverage, sporadic diphtheria outbreaks still occur. The rising trend of cases reported over the recent years underscores the need to remain vigilant. Addressing pockets of unvaccinated children and potential waning immunity levels in the population remains pivotal.

Non-toxigenic Corynebacterium diphtheriae in hallux ulceration.

INTRODUCTION: Toxigenic Corynebacterium diphtheriae causes classical diphtheria. Skin infections by toxigenic or non-toxigenic Corynebacterium diphtheriae are prevalent in the tropics but are rarely reported. CASE PRESENTATION: We report the identification of a non-toxigenic Corynebacterium diphtheriae (biovar Gravis) isolate in a 52-year-old Cambodian male. The patient presented purulent and non-healing ulcerations on the right hallux. The wound has healed after 7 days of antibiotic therapy with a favourable outcome. CONCLUSIONS: This case represents, to our knowledge, the first report of Corynebacterium diphtheriae in Cambodia in the last 10 years, and highlights the lack of diagnosis and notifications of diphtheria. It is important to raise awareness among clinicians and to set up diphtheria surveillance in Cambodia.