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In this article, we have developed a deterministic Susceptible-Latent-Infectious-Recovered (SLIR) model for diphtheria outbreaks. Here, we have studied a case of the diphtheria outbreak in the Rohingya refugee camp in Bangladesh to trace the disease dynamics and find out the peak value of the infection. Both analytical and numerical investigations have been performed on the model to find several remarkable behaviors like the positive and bounded solution, basic reproductive ratio, and equilibria such as disease extinction equilibrium and disease persistence equilibrium which are characterized depending on the basic reproductive ratio and global stability of the model using Lyapunov function for both equilibria. Parameter estimation has been performed to determine the values of the parameter from the daily case data using numerical technique and determined the value of the basic reproductive number for the outbreak as ℛ 0 = 5.86., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zahurul Islam et al.)

In some parts of the world, Corynebacterium diphtheriae has reemerged as a pathogen, especially as a cause of infections among impoverished and marginalized populations. We performed whole-genome sequencing (WGS) on all cutaneous C. diphtheriae isolates ( n  = 56) from Vancouver's inner-city population over a 3-year time period (2015 to 2018). All isolates with complete genome assembly were toxin negative, contained a common set of 22 virulence factors, and shared a highly conserved accessory genome. One of our isolates harbored a novel plasmid conferring macrolide and lincosamide resistance. Fifty-two out of 56 isolates were multilocus sequence type 76, and single nucleotide variants (SNV) and core-genome multilocus sequence typing (cgMLST) analysis demonstrated tight clustering of our isolates relative to all publicly available C. diphtheriae genomes. All sequence type 76 (ST76) study isolates were within a median of 22 SNVs and 13 cgMLST alleles of each other, while NCBI genomes were within a median of 17,436 SNVs and 1,552 cgMLST alleles of each other (both P  < 2.2 × 10 -16 ). A single strain of C. diphtheriae appears to be causing cutaneous infections in the low-income population of Vancouver. Further research is needed to elucidate transmission networks in our study population and standardize C. diphtheriae epidemiological typing when whole genomes are sequenced., (Copyright © 2020 American Society for Microbiology.)

Most people know little about diphtheria today thanks to the effectiveness of its vaccine. But fear of this highly contagious bacterial infection - which chokes off patients' ability to breathe - was once so strong that it accidentally gave birth to a major sporting event: the Iditarod Trail Dog Sled Race.

Endemic transmission of measles has been reestablished in Venezuela, and outbreaks of diphtheria remain ongoing across Latin America (LA). Hence, a large cross-sectional population-based serosurveillance study was conducted on Bonaire, one of the Dutch Leeward Antilles, to assess specific age and population groups at risk. Participants (aged 0-90 years) donated a blood sample and completed a questionnaire ( n = 1,129). Antibodies against measles and diphtheria were tested using bead-based multiplex immunoassays. Our data revealed that immunity against measles is suboptimal, especially for those aged less than 5 years from Suriname, Aruba, and former Dutch Antilles (SADA), and adolescents from LA; and against diphtheria for persons aged more than 30 years, particularly among females and residents from SADA and LA. As refugees arrive persistently, health authorities on the Dutch Leeward Antilles should be on alert to detect early cases and prevent subsequent transmission. Ultimately, there is an urgent need for serosurveillance studies in the Caribbean region.

Cystic fibrosis (CF) patients are commonly colonized by bacterial pathogens, which can induce persistent lung inflammation and may contribute to clinical deterioration. Colonization of CF patients and cross-transmission by Corynebacterium diphtheriae have not been reported so far. The aim of this article was to investigate the possibility of a cross-transmission of C. diphtheriae biovar Belfanti between four patients of a CF center. C. diphtheriae biovar Belfanti (now formally called C. belfantii ) isolates were collected from four patients in a single CF care center over a period of 6 years and analyzed by microbiological methods and whole-genome sequencing. Epidemiological links among patients were investigated. Ten isolates were collected from 4 patients. Whole-genome sequencing of one isolate from each patient showed that a single strain was shared among them. In addition, one patient was found to have the same strain in two consecutive samplings performed 9 months apart. The strain was nontoxigenic and was susceptible to most antimicrobial agents. Ciprofloxacin resistance was observed in one patient. The idea of transmission of the strain among patients was supported by the occurrence of same-day visits to the CF center. This study demonstrated colonization of CF patients by C. diphtheriae biovar Belfanti ( C. belfantii ), and the data suggest persistence and transmission of a unique strain during at least 6 years in a single CF patient care center., (Copyright © 2019 American Society for Microbiology.)

Background: Diphtheria toxin (DT) is produced by toxigenic strains of the human pathogen Corynebacterium diphtheriae as well as zoonotic C. ulcerans and C. pseudotuberculosis. Toxigenic strains may cause severe respiratory diphtheria, myocarditis, neurological damage or cutaneous diphtheria. The DT encoding tox gene is located in a mobile genomic region and tox variability between C. diphtheriae and C. ulcerans has been postulated based on sequences of a few isolates. In contrast, species-specific sequence analysis of the diphtheria toxin repressor gene (dtxR), occurring both in toxigenic and non-toxigenic Corynebacterium species, has not been done yet. We used whole genome sequencing data from 91 toxigenic and 46 non-toxigenic isolates of different pathogenic Corynebacterium species of animal or human origin to elucidate differences in extracted DT, DtxR and tox-surrounding genetic elements by a phylogenetic analysis in a large sample set., Results: Sequences of both DT and DtxR, extracted from whole genome sequencing data, could be classified in four distinct, nearly species-specific clades, corresponding to C. diphtheriae, C. pseudotuberculosis, C. ulcerans and atypical C. ulcerans from a non-toxigenic toxin gene-bearing wildlife cluster. Average amino acid similarities were above 99% for DT and DtxR within the four groups, but lower between them. For DT, subgroups below species level could be identified, correlating with different tox-comprising mobile genetic elements. In most C. diphtheriae, tox genes were located within known prophages. In contrast, in C. ulcerans diverse tox-including mobile elements could be identified: either prophages differing from C. diphtheriae prophages or an alternative pathogenicity island (PAI) described previously. One isolate showed a different, shorter tox-comprising putative PAI. Beyond the tox-overlapping elements, most isolates harbored a variety of additional prophages., Conclusion: Our NGS data from 137 isolates indicate the existence of different genetic backgrounds of DT-mediated pathogenicity in different Corynebacterium species and evolution of once acquired pathogenicity features with the strains. Different groups of pathogenicity-related elements within C. ulcerans imply that tox transmission pathways between isolates may differ in the zoonotic species and contribute to their emerging pathogenic potential.

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child's sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae . Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.

We report a fatal autochthonous diphtheria case in a migrant worker in Singapore. This case highlights the risk for individual cases in undervaccinated subpopulations, despite high vaccination coverage in the general population. Prompt implementation of public health measures and maintaining immunization coverage are critical to prevent reemergence of diphtheria.

In this work, a mathematical model for describing diphtheria transmission in Thailand is proposed. Based on the course of diphtheria infection, the population is divided into 8 epidemiological classes, namely, susceptible, symptomatic infectious, asymptomatic infectious, carrier with full natural-acquired immunity, carrier with partial natural-acquired immunity, individual with full vaccine-induced immunity, and individual with partial vaccine-induced immunity. Parameter values in the model were either directly obtained from the literature, estimated from available data, or estimated by means of sensitivity analysis. Numerical solutions show that our model can correctly describe the decreasing trend of diphtheria cases in Thailand during the years 1977-2014. Furthermore, despite Thailand having high DTP vaccine coverage, our model predicts that there will be diphtheria outbreaks after the year 2014 due to waning immunity. Our model also suggests that providing booster doses to some susceptible individuals and those with partial immunity every 10 years is a potential way to inhibit future diphtheria outbreaks., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007-2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans , with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery., (2017 BMJ Publishing Group Ltd.)

Diphtheria is a debilitating disease caused by toxigenic Corynebacterium diphtheriae strains and has been effectively controlled by the toxoid vaccine, yet several recent outbreaks have been reported across the globe. Moreover, non-toxigenic C. diphtheriae strains are emerging as a major global health concern by causing severe pharyngitis and tonsillitis, endocarditis, septic arthritis and osteomyelitis. Molecular epidemiological investigations suggest the existence of outbreak-associated clones with multiple genotypes circulating around the world. Evolution and pathogenesis appears to be driven by recombination as major virulence factors, including the tox gene and pilus gene clusters, are found within genomic islands that appear to be mobile between strains. The number of pilus gene clusters and variation introduced by gain or loss of gene function correlate with the variable adhesive and invasive properties of C. diphtheriae strains. Genomic variation does not support the separation of C. diphtheriae strains into biovars which correlates well with findings of studies based on multilocus sequence typing. Genomic analyses of a relatively small number of strains also revealed a recombination driven diversification of strains within a sequence type and indicate a wider diversity among C. diphtheriae strains than previously appreciated. This suggests that there is a need for increased effort from the scientific community to study C. diphtheriae to help understand the genomic diversity and pathogenicity within the population of this important human pathogen., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)

Toxigenic Corynebacterium ulcerans is an emerging cause of diphtheria. In contrast to the classical diphtheria pathogen C. diphtheriae, human-to-human transmission of this primarily zoonotic pathogen has not been clearly documented. Here we report on a two-person cluster suggesting an initial zoonotic and a subsequent human-to-human transmission event., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

On 12 June 2015, Corynebacterium diphtheriae was identified in a skin swab from a burns patient in Scotland. The isolate was confirmed to be genotypically and phenotypically toxigenic. Multilocus sequence typing of three patient isolates yielded sequence type ST 125. The patient was clinically well. We summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for C. diphtheriae.

Reports on cases of human diphtheria caused by toxigenic Corynebacterium ulcerans that were linked to occupational swine contact as well as isolation of C ulcerans from wild boars have suggested that pigs might serve as reservoir for human infections. Therefore, a prevalence study on Corynebacterium species nasal carriage in pigs and their farmers was performed between August 1 and December 31, 2009, in 41 swine farms from Bavaria, Germany. All 411 asymptomatic pigs and 29 of 30 healthy farmers were colonised with Corynebacterium strains of up to 11 different species. No potentially toxigenic Corynebacterium strain was isolated either from the pigs or from their farmers, respectively. The patterns of the species composition in the pigs and the farmers were very similar, suggesting a potential transmission of strains between animals and humans., (British Veterinary Association.)

Diphtheria is caused by diphtheria toxin-producing Corynebacterium species. While classical respiratory diphtheria is transmitted by droplets, cutaneous diphtheria often results from minor trauma. This report concerns the first case of sexually transmitted diphtheria in a patient with non-gonococcal urethritis after orogenital contact.

Aim: Diphtheria is an acute bacterial illness caused by toxigenic strains of Corynebacterium diphtheriae (C. diphtheriae). We describe two epidemiologically-linked cases of skin infections from which toxigenic C. diphtheriae was isolated, and discuss implications for diphtheria surveillance and management in New Zealand., Method: A public health investigation was undertaken to identify and manage close contacts of the index case. National and international guidelines on the surveillance and management of cutaneous diphtheria were reviewed, and data on toxigenic C. diphtheriae isolates identified in New Zealand from 1987-2009 were examined., Results: The index case was an adult male who developed a cutaneous infection after being tattooed in Samoa. A wound swab taken from the infected tattoo grew a toxigenic strain of C. diphtheriae (var gravis). A secondary case of toxigenic cutaneous diphtheria was identified in a household contact. Instances of respiratory diphtheria associated with toxigenic cutaneous lesions have been reported in the literature. The review of surveillance data revealed inconsistencies in the notification of toxigenic strains of C. diphtheriae isolated from cutaneous sites., Conclusion: These cases are an important reminder that diphtheria remains a threat in New Zealand. All cases with toxigenic C. diphtheriae isolated from a clinical specimen, regardless of the site of infection, should be notified to a Medical Officer of Health.

We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterinary student, investigated in London, United Kingdom, in May 2010. There was no ongoing transmission in human contacts. Possible animal sources were identified.

While many works have examined urban mortality rates in nineteenth-century Europe, much less attention has been placed on disease patterns in the peripheral areas surrounding these population centers. This study demonstrates that during the Swedish diphtheria epidemic of the early 1880s, mortality rates among children living in the industrial parishes on the outskirts of the town of Sundsvall exceeded those found in the town itself. The epidemic was fueled by the mass in-migration of laborers and their families from distant provinces who sought work in the region's sawmills. Thus, in contrast to the common pattern of disease entering through a port city and spreading into the interior, in this case diphtheria followed the paths of migrants through the rural parishes of the Sundsvall region to the sawmills and then finally into the town itself. This spatial pattern was reversed in the late fall when migrants returned home. Conflicts within the medical profession regarding how best to prevent or contain diphtheria, popular suspicion and distrust of local physicians, and the introduction of the disease into a population with no prior contact with it, all helped increase the number of young corpses.

For infection control in pediatric hospitals, we investigated the risk of pertussis and diphtheria infections among pediatric healthcare workers. Forty-nine Japanese pediatric healthcare workers in 12 general hospitals were screened for antibodies of pertussis toxin (PT), filamentous hemagglutinin (FHA), and diphtheria toxin (DT). The seropositive rates of anti-PT IgG (protective level, > 10 U/mL), anti-FHA IgG (> 10 U/ mL), and anti-DT (> 0.11 U/mL) were 50, 82, and 59%, respectively. During this survey period (Oct. 2003-Feb. 2004), 16 (33%) of the healthcare workers were in contact with pertussis-infant (s). However, all culture and PCR tests for Bordetella pertussis were negative. One of the 16 exposed healthcare workers, a male pediatrician, had serological evidence of a pertussis infection, but no disease symptomatic of pertussis. Our observations indicate that i) 50 and 41% of Japanese pediatric healthcare workers were seronegative for pertussis (anti-PT IgG) and diphtheria antibodies, respectively, and ii) although the healthcare workers had a high rate of contact with pertussis-infant (s), the infection rate was low. For pertussis and diphtheria infection control in pediatric hospitals, it is important for healthcare workers to be aware of their own protection levels against these diseases.

Introduction: Pseudomembranous angina are classically caused by Corynebacterium diphtheriae. More rarely, it caused by Corynebacterium ulcerans, sometimes carrying the diphteric exotoxine. EXEGERIS: We report a new autochton case of pseudomembranous pharyngitis caused by C. ulcerans, carrying the diphteric exotoxine, transmitted by a dog, complicated of velopharyngitis and hypopharyngée paralysis, then of diphtheric polyneuritis., Conclusion: Although exceptional, diphteria must always be evoked in front of a pseudomembranous angina. The insolation of C. ulcerans must make seek diphteric toxin and its complications.

In their mathematical description of vaccine-induced immunity, Gandon et al. predict that the host's immunity to a microbial toxin will lead to increased virulence of the pathogen without affecting its transmission. However, results obtained using vaccines against two additional bacterial pathogens are not consistent with this prediction. The model proposed by Gandon et al. may therefore be an oversimplification, with the outcome depending on the biological details of both the pathogen and the vaccine.

During the 1990-1998 diphtheria epidemic in the newly independent states of the former Soviet Union, more than 150,000 infections and 5,000 deaths occurred. During this period, more than 10 million trips were made from Finland to Russia or vice versa. This resulted in only 10 cases of diphtheria in Finland. There was no secondary spread to healthcare workers or other close contacts. Three patients had severe respiratory tract diphtheria. All three were middle-aged men who had made a short visit to Russia, during which time they had intimate contact with local women. These findings suggest diphtheria was transmitted mainly by direct saliva contact. All patients with severe diphtheria had a non-protective level of antitoxin antibodies during the first days of the disease. Only the patient whose antibody titre rose rapidly to a protective level (>1 IU/ml) had an uncomplicated recovery. The other two, one of whom died, had myocarditis and severe polyneuropathy.

The large-scale resurgence of diphtheria in the former Soviet Union offered a unique opportunity to evaluate risk factors for the transmission of respiratory diphtheria; therefore, a prospective case-control study was done in the republic of Georgia. In total, 218 diphtheria cases (hospitalized between October 1995 and March 1996) and 408 matched controls participated. One hundred cases (45%) were /=15 years of age (range: <1 to 75 years). In the multivariate analyses, the following risk factors were found to be significant: lack of vaccination (matched odds ratio [mOR]=19.2), household exposure to diphtheria (mOR=7.4), exposure to skin lesions (mOR=5.8), history of eczema (mOR=3.4), fever with myalgia prior to illness (mOR=2.6), having tonsils (mOR=4.4), sharing a bed (mOR=1.9), sharing cups and glasses (mOR=2.7), and taking a bath less than once a week (mOR=2.6). These findings emphasize primary prevention through immunizations, secondary prevention following exposure to diphtheria (and to suspicious skin lesions), and adherence to strict standards of personal hygiene.

The causative agent for diphtheria is Corynebacterium diphtheriae, which is transmitted from person to person from the throat of carriers or from patients with active cutaneous diphtheria. The disease occurs in preexisting ulcers, but it may also appear on apparently normal skin. Although primary cutaneous diphtheria starts as a vesicle or pustule, most patients feature a reddish ulcer with undermined borders. The lesion is tender but hypesthesia develops after 2 weeks. The clinical diagnosis is based on the history of travelling in endemic regions and bacteriological studies. The current increase of diphtheria in the Western world is partly caused by rising tourism and a decline of booster vaccination in adults. After trauma with ulcerations of the skin we suggest to perform a booster vaccination not only for tetanus but also for diphtheria. In addition, persons travelling to endemic regions should receive a booster vaccination for tetanus and diphtheria, which is available as a combined preparation.

A 43-year-old woman, born in the Netherlands, developed ulcers on her left foot during a holiday in Gambia and Senegal. She had been bitten bij insects. The ulcers were caused by Corynebacterium diphtheriae. The patient was treated with antibiotics and recovered fully. A grey pseudomembrane covering the ulcer is a characteristic feature of cutaneous diphtheria. The treatment is with antibiotics and, after toxin tests have indicated that the bacterium is toxigenic, with antitoxin. In some cases screening of social contacts is advised.

Blood samples from 171 full-term pregnant women (aged 18-38 years) of middle socioeconomic status from Delhi were tested for diphtheria antitoxins by indirect hemagglutination (IHA) test. History of primary immunization/clinical diphtheria during childhood was not ascertainable, but none had been revaccinated against diphtheria at any time. About 94% women had very high antitoxin titers (> or = 0.125 IU/ ml); none had antitoxin titer less than 0.015 IU/ml, the minimum protective level. The titers were uniformly high in all age groups. However, women having 2 or more children had significantly higher antitoxin titers than those having no or one child (p < 0.01). The results from this study and historical data on diphtheria in Delhi are compatible with continued transmission of C. diphtheriae in recent times in Delhi which is of sufficient magnitude to boost the antitoxin levels in adults, especially mothers having two or more children. The study highlights the need of increasing the immunization coverage with DPT among children to reduce the transmission of Corynebacterium diphtheriae.

In the present study we report the results of an analysis, based on ribotyping of Corynebacterium diphtheriae intermedius strains isolated from a 9 years old child with clinical diphtheria and his 5 contacts. Quantitative analysis of RFLPs of rRNA was used to determine relatedness of these 7 C.diphtheriae strains providing support data in the diphtheria epidemiology. We have also tested those strains for toxigenicity in vitro by using the Elek's gel diffusion method and in vivo by using cell culture method on cultured monkey kidney cell (VERO cells). The hybridization results revealed that the 5 C.diphtheriae strains isolated from contacts and one isolated from the clinical case (nose case strain) had identical RFLP patterns with all 4 restriction endonucleases used, ribotype B. The genetic distance from this ribotype and ribotype A (throat case strain), that we initially assumed to be responsible for the illness of the patient, was of 0.450 showing poor genetic correlation among these two ribotypes. We found no significant differences concerned to the toxin production by using the cell culture method. In conclusion, the use of RFLPs of rRNA gene was successful in detecting minor differences in closely related toxigenic C.diphtheriae intermedius strains and providing information about genetic relationships among them.