Diphtheria in a Swiss Asylum Seeker Reception Centre: Outbreak Investigation and Evaluation of Testing and Vaccination Strategies.

Objectives: To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. Methods: We retrospectively analysed clinical, microbiology, and case management data of all asylum seekers tested for C. diphtheriae between 28th August and 31st December 2022 while residing at the centre. Results are reported descriptively. Results: Among 265 individuals tested, ten cases of cutaneous diphtheria, one simultaneous respiratory and cutaneous case, and nine respiratory carriers were identified. Mass throat screening, targeted throat testing and targeted wound testing yielded 4.8%, 4.3%, and 17.4% positive results, respectively. No respiratory carrier was identified among cutaneous cases undergoing a throat swab, and no symptomatic case was identified among individuals with unspecific throat symptoms. Rates of vaccination implementation of newly arriving asylum seekers before and after the outbreak were low (17.5% and 15.5%, respectively), as were rates of targeted vaccination among cases and close contacts. Conclusion: We provide evidence for transmission both prior to arrival and within the setting, suboptimal practices and timeliness of testing, and implementation gaps in vaccination.

Cluster of Nontoxigenic Corynebacterium diphtheriae Infective Endocarditis and Rising Background C. diphtheriae Cases-Seattle, Washington, 2020-2023.

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.

Pastern dermatitis outbreak associated with toxigenic and non-toxigenic Corynebacterium diphtheriae and non-toxigenic Corynebacterium ulcerans at a horse stable in Finland, 2021.

AIMS: Corynebacterium diphtheriae and Corynebacterium ulcerans, when producing toxin, are the cause of diphtheria, a potentially life-threatening illness in humans. Horses (Equus ferus caballus) are known to be susceptible to infection that may manifest clinically on rare occasions. In late 2021 and early 2022, specimens from five horses suffering from pastern dermatitis were cultured at the Laboratory of Clinical Microbiology at the Faculty of Veterinary Medicine, University of Helsinki, Finland. C. diphtheriae and/or C. ulcerans were recovered from all of these. This study aimed to (1) analyse the bacterial isolates and (2) describe the outbreak and identify possible sources of the infection and infection routes in the stable. METHODS AND RESULTS: Susceptibility testing, PCR for the tox gene, and Elek test for toxin production in PCR-positive isolates were performed. Whole genome sequencing was also conducted to achieve high-resolution strain typing. An epidemiological survey was done by means of a semi-structured interview of horses' caretaker, and contact tracing was done among people at the stable. Two tox gene-positive, toxin-producing C. diphtheriae belonged to sequence type (ST) 822. Other C. diphtheriae (n = 2, ST828) and C. ulcerans (n = 2, ST325 and ST838) isolates did not carry the tox gene. The epidemiological investigation explored numerous possible routes of transmission, but the definite source of infection was not identified. All established human contacts tested negative for diphtheriae. All horses recovered after antimicrobial treatment. CONCLUSIONS: Our study shows that C. diphtheriae and C. ulcerans may readily spread among horses at the same stable and complicate pastern dermatitis infections. These potentially zoonotic bacteria can cause outbreaks even in a country with a very low prevalence. Caretakers should be encouraged to wear gloves and practice good hand hygiene when treating infected skin lesions in horses.

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.

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.

Recurrent diphtheria outbreaks in Nigeria: A review of the underlying factors and remedies.

INTRODUCTION: The introduction of the diphtheria-tetanus-pertussis (DTP) vaccine into childhood immunization programs resulted in its widespread elimination in high-income countries. However, Nigeria is currently experiencing an outbreak. The primary cause of diphtheria outbreaks and its high mortality rates in Nigeria was waning herd immunity due to low DTP coverage and a lack of diphtheria antitoxin (DAT), respectively. However, the underlying causes of Nigeria's low DTP coverage and DAT supply remain unknown. METHOD: Relevant studies and reports included in our review were obtained by a search through Google Scholar, PubMed, and organization websites using the terms "Diphtheria-Pertussis-Tetanus vaccine OR Diphtheria antitoxin and Nigeria OR Diphtheria Outbreak." All articles considering diphtheria outbreaks, DTP vaccine, and DAT supply in Nigeria were considered without time restriction due to the paucity of data. We used the narrative synthesis approach to critically appraise, analyze, and draw inferences from the selected articles. RESULTS: The main causes of low DTP coverage are insufficient supply, an inefficient cold chain system, and low uptake due to poor health literacy and negative sociocultural and religious beliefs, whereas the key barriers to DAT availability are insufficient production by pharmaceutical industries because of low demand and priority. CONCLUSION: The underlying causes of Nigeria's low DTP coverage and DAT supply are multifactorial. Both short-term and long-term measures are needed to control this outbreak and prevent future occurrences.

A looming epidemic: combating the recurrent outbreaks of diphtheria in Nigeria.

Nigeria has endured several diphtheria outbreaks over the last few decades, mirroring a suboptimal population immunity across several demographics within the country. The country's northern region has been affected mainly by this infectious disease; it directly depicts the effect of poor DPT vaccine uptake amongst children in this region compared to other geopolitical zones in Nigeria. Whilst pharmaceutical intervention and surveillance activities have commenced as directed by the NCDC, to combat this public health menace, top leaders of the Nigerian healthcare system - public and private sectors, must understudy the predisposing factors gearing the recurrence of diphtheria in Nigeria and provide robust, research-based and scientific mechanisms to arrest the root causes of the incessant outbreaks. This article discusses the factors promoting the recurrent diphtheria outbreaks in Nigeria, the preexisting interventions with their existential deterrents, and new strategies recommended to curb the further resurgence of the disease.

Several confirmed and probable zoonotic cases of toxigenic Corynebacterium ulcerans, Queensland, Australia.

Background: Toxigenic Corynebacterium ulcerans is an emerging zoonosis globally, causing both cutaneous and respiratory diphtheria-like illness. In Queensland, human infection with toxigenic C. ulcerans is rare, with only three cases reported before October 2015. This case series describes five subsequent cases of toxigenic C. ulcerans in Queensland with links to companion animals. Methods: All data were collected as part of routine public health response, and strains were whole genome sequenced for further characterisation. Household contacts were screened, treated with appropriate antibiotics, and received a diphtheria toxoid-containing vaccine if more than five years had elapsed since their last dose. Findings: No epidemiological or genomic links could be established between any of the five patients, including between the two cases notified from the same locality within eight days of each other. The C. ulcerans strains from Cases Two, Four and Five were closely related to the strains isolated from their respective pets by whole genome sequencing. Domestic dogs were identified as the most likely mode of transmission for Cases One and Three; however, this was unable to be laboratory confirmed, since Case One's dog was treated with antibiotics before it could be tested, and Case Three's dog was euthanised and cremated prior to case notification. Interpretation: These are the first reported Australian cases of this emerging zoonosis with links to companion animals. These cases demonstrate the likely transmission route between companion animals and humans, with no evidence of human-to-human transmission. The existing requirement in the Queensland Health Public Health Management Guidelines, of restrictions on cases and some contacts while awaiting swab results, is currently under review.

Genomic characterization of cocirculating Corynebacterium diphtheriae and non-diphtheritic Corynebacterium species among forcibly displaced Myanmar nationals, 2017-2019.

Respiratory diphtheria is a serious infection caused by toxigenic Corynebacterium diphtheriae, and disease transmission mainly occurs through respiratory droplets. Between 2017 and 2019, a large diphtheria outbreak among forcibly displaced Myanmar nationals densely settled in Bangladesh was investigated. Here we utilized whole-genome sequencing (WGS) to characterize recovered isolates of C. diphtheriae and two co-circulating non-diphtheritic Corynebacterium (NDC) species - C. pseudodiphtheriticum and C. propinquum. C. diphtheriae isolates recovered from all 53 positive cases in this study were identified as toxigenic biovar mitis, exhibiting intermediate resistance to penicillin, and formed four phylogenetic clusters circulating among multiple refugee camps. Additional sequenced isolates collected from two patients showed co-colonization with non-toxigenic C. diphtheriae biovar gravis, one of which exhibited decreased susceptibility to the first-line antibiotics and harboured a novel 23-kb multidrug resistance plasmid. Results of phylogenetic reconstruction and virulence-related gene contents of the recovered NDC isolates indicated they were likely commensal organisms, though 80.4 %(45/56) were not susceptible to erythromycin, and most showed high minimum inhibition concentrations against azithromycin. These results demonstrate the high resolution with which WGS can aid molecular investigation of diphtheria outbreaks, through the quantification of bacterial genetic relatedness, as well as the detection of virulence factors and antibiotic resistance markers among case isolates.

National public health response to an outbreak of toxigenic Corynebacterium diphtheriae among asylum seekers in England, 2022: a descriptive epidemiological study.

BACKGROUND: In July, 2022, an increase in diphtheria cases caused by toxigenic Corynebacterium diphtheriae (C diphtheriae) was reported among asylum seekers arriving by small boats to England. Rising case numbers presented challenges for case and contact management in initial reception centres, prompting changes to national guidance and implementation of population-based control measures. This study aimed to describe the outbreak of toxigenic C diphtheriae among asylum seekers arriving by small boats to England during 2022 by use of national surveillance data. METHODS: We undertook a descriptive epidemiological analysis of cases of toxigenic C diphtheriae among asylum seekers arriving by small boats to England during 2022, incorporating genomic sequencing data, antibiotic susceptibility testing results, and epidemiological data obtained through the UK Health Security Agency's national enhanced surveillance programme. Health Protection Teams conducted risk assessments, and operational data (including details regarding offer and uptake of antibiotics and vaccinations) were obtained from National Health Service partners supporting the intervention programme. FINDINGS: In 2022, C diphtheriae isolates from 86 asylum seekers arriving by small boats were submitted to the National Reference Laboratory for confirmation and testing. Toxigenic C diphtheriae was confirmed for 72 (84%) cases and one individual with typical diphtheritic lesions but from whom no C diphtheriae was isolated from clinical swabs was also included as a probable case, resulting in 73 cases of diphtheria. 71 (97%) were male, 39 (53%) were younger than 18 years, and 36 (49%) presented with cutaneous diphtheria. The prevalence of diphtheria was highest among Afghans (1·3%) compared with all other nationalities (<0·1%). Local antibiotic susceptibility testing identified six cases with a macrolide resistant strain. INTERPRETATION: The increase in diphtheria coincided with a high volume of asylum seekers arriving by small boats to England during 2022, and subsequently increased clinical awareness of the disease among this population. Long-term disruption to vaccination programmes in origin countries along with barriers to accessing health care along migrant routes puts asylum seekers arriving by small boats at risk of disease. With arrivals expected to continue in 2023, the UK Health Security Agency has recommended continuation of population-based control measures in England until October, 2023, subject to ongoing review. FUNDING: The UK Health Security Agency.

Estimation of vaccination coverage and associated factors in older Mexican adults.

National vaccination programmes recommend the influenza vaccine for older adults, but this population group has the greatest morbidity and mortality from other preventable vaccine diseases. The aim of this article is to estimate the vaccine coverage in adults aged 65 years and older and to analyse the factors that could increase or decrease vaccination uptake probability for the three listed vaccines in the national vaccination programme (influenza, tetanus and diphtheria, and pneumococcus) and the full scheme in Mexico. We conducted an analytical cross-sectional study with 2012, 2018, and 2021 rounds from the National Health and Nutrition Survey, in which we calculated the vaccine coverage estimations and performed multivariable logistic regression models to analyse the factors related to vaccine uptake. Tetanus and diphtheria vaccines had the greatest coverage estimation in all years (59-71%), whereas the pneumococcus vaccine had the lowest (32-53%). Full scheme vaccine coverage decreased from 37.80% to 24.77% in 2012 and 2021, respectively. The National Health Card property, morbidity, being a beneficiary of any health system institution, and use of preventive services increased the probability of vaccine uptake. In conclusion, vaccine coverage in older Mexican adults decreased over time, and the Mexican health system plays a strategic role in immunisation.

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.