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Background Ensuring vaccination coverage reaches established herd immunity thresholds (HITs) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPDs) and outbreaks, yet it is not clear to what extent they are an under-immunized group. Methods We did a systematic review and meta-analysis to synthesize peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (1 January 2000 to 10 June 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666). Findings Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n  = 7, 57.4% [95% confidence interval (CI): 43.1–71.7%] I 2 = 99% vs HIT 83–86%), measles (n  = 21, 83.7% [95% CI: 79.2–88.2] I 2 = 99% vs HIT 93–95%) and mumps (n  = 8, 67.1% [95% CI: 50.6–83.6] I 2 = 99% vs HIT 88–93%) and midway for rubella (n  = 29, 85.6% [95% CI: 83.1–88.1%] I 2 = 99% vs HIT 83–94%), with high heterogeneity across studies. Interpretation Migrants in Europe are an under-immunized group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life course in under-immunized groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity. [ABSTRACT FROM AUTHOR]

Human infections with Corynebacterium diphtheriae species complex (CdSC) bacteria were rare in French Guiana until 2016, when the number of cases diagnosed increased. We conducted an epidemiologic, multicenter, retrospective study of all human CdSC infections diagnosed in French Guiana during January 1, 2016–December 31, 2021. A total of 64 infectious episodes were observed in 60 patients; 61 infections were caused by C. diphtheriae and 3 by C. ulcerans. Estimated incidence increased from 0.7 cases/100,000 population in 2016 to 7.7 cases/100,000 population in 2021. The mean patient age was 30.4 (+23.7) years, and male-to-female ratio was 1.7:1 (38/22). Of the 61 C. diphtheriae isolates, 5 tested positive for the diphtheria toxin gene, and all results were negative by Elek test; 95% (61/64) of cases were cutaneous, including the C. ulcerans cases. The increase in reported human infections underscores the need to raise awareness among frontline healthcare practitioners to improve prevention.

Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in the microbiological diagnosis of diphtheria and other corynebacteria infections. Since the first demonstration in 1888 that DT is a major virulence factor of C. diphtheriae, responsible for the systemic manifestation of the disease, various methods for DT detection have been developed, but the diagnostic usefulness of most of them has not been confirmed on a sufficiently large group of samples. Despite substantial progress in the science and diagnostics of infectious diseases, the Elek test is still the basic recommended diagnostic test for DT detection. The challenge here is the poor availability of an antitoxin and declining experience even in reference laboratories due to the low prevalence of diphtheria in developed countries. However, recent and very promising assays have been developed with the potential for use as rapid point-of-care testing (POCT), such as ICS and LFIA for toxin detection, LAMP for tox gene detection, and biosensors for both. [ABSTRACT FROM AUTHOR]

Background: Diphtheria can be prevented by vaccination, but some epidemics occur in several places, and diphtheria's threat is considerable. Administration of diphtheria antitoxin (DAT) produced from hyperimmunized animals is the most common treatment. Recombinant human antibody fragments such as single-chain variable fragments (scFv) produced by phage display library may introduce an interesting approach to overcome the limitations of the traditional antibody therapy. In the present study, B cells of immunized volunteers were used to construct a human single-chain fragment (HuscFv) library. Materials and methods: The library was constructed with the maximum combination of heavy and light chains. As an antigen, Diphtheria toxoid (DTd) was used in four-round phage bio-panning to select phage clones that display DTd bound HuscFv from the library. After panning, individual scFv clones were selected. Clones that were able to detect DTd in an initial screening assay were transferred to Escherichia coli HB2151 to express the scFvs and purification was followed by Ni metal ion affinity chromatography. Toxin neutralization test was performed on Vero cells. The reactivity of the soluble scFv with diphtheria toxin were done and affinity calculation based on Beatty method was calculated. Results: The size of the constructed scFv library was calculated to be 1.3 × 106 members. Following four rounds of selection, 40 antibody clones were isolated which showed positive reactivity with DTd in an ELISA assay. Five clones were able to neutralize DTd in Vero cell assay. These neutralizing clones were used for soluble expression and purification of scFv fragments. Some of these soluble scFv fragments show neutralizing activity ranging from 0.6 to 1.2 µg against twofold cytotoxic dose of diphtheria toxin. The affinity constant of the selected scFv antibody was determined almost 107 M−1. Conclusion: This study describes the prosperous construction and isolation of scFv from the immune library, which specifically neutralizes diphtheria toxin. The HuscFv produced in this study can be a potential candidate to substitute the animal antibody for treating diphtheria and detecting toxins. [ABSTRACT FROM AUTHOR]

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Evidence-based clinical susceptibility breakpoints have been lacking for antimicrobial agents used for diphtheria. Objectives We aimed to evaluate broth microdilution and disc diffusion methods and create a dataset of MIC values and inhibition zone diameters (ZDs) from which breakpoints could be determined. Methods We included 400 recent clinical isolates equally distributed by species (Corynebacterium diphtheriae and Corynebacterium ulcerans) and by national surveillance programmes (France and Germany). Non-duplicate toxigenic and non-toxigenic isolates were chosen to enable the inclusion of a diversity of susceptibility levels for the 13 agents tested. Broth microdilution and disc diffusion, using EUCAST methodology for fastidious organisms, were used. Results The distributions of MIC and ZD values were largely in agreement among methods and countries. Breakpoints to allow categorization of WT isolates as susceptible, i.e. susceptible (S) or susceptible, increased exposure (I) were determined for 12 agents. The data supported a breakpoint for benzylpenicillin and amoxicillin of resistant (R) > 1 mg/L since WT isolates were inhibited by 1 mg/L or less. WT isolates were categorized as I (S ≤ 0.001 mg/L) for benzylpenicillin, emphasizing the need for increased exposure, and S (S ≤ 1 mg/L) for amoxicillin. Erythromycin breakpoints were set at S ≤ 0.06 mg/L and R > 0.06 mg/L. The corresponding ZD breakpoints were determined for all agents except amoxicillin, for which categorization was based on benzylpenicillin results. Conclusions This work provided a large set of antimicrobial susceptibility data for C. diphtheriae and C. ulcerans , using a harmonized methodology. The dataset allowed EUCAST and experts in the diphtheria field to develop evidence-based breakpoints in January 2023. [ABSTRACT FROM AUTHOR]

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Background: With the increase in immunosuppressed patients and antimicrobial misuse, Non-diphtheriae Corynebacterium species (NDC spp.) have risen as opportunistic pathogens in hospitalized patients. The current work aimed at comparing Vitek 2C automated identification cards versus MALDI-TOF (Matrix-associated laser-induced desorption ionization-time of flight) as the gold standard method for the identification of different NDC spp. and determining the antimicrobial susceptibility of NDC spp. by the disc diffusion method for proper management of patients. Methods: Thirty NDC spp. isolates were subjected to identification by MALDI-TOF MS and Vitek 2C and antibiotic susceptibility testing by the disc diffusion method. Results: Our study showed that Corynebacterium (C.) striatum was the most commonly isolated species (83.3%), followed by C. amycolatum (10%). 36.7 % of the isolates were recovered from blood culture while 20 % were recovered from deep wounds. As regard isolate identification by Vitek-2C ANC ID CARD compared to MALDI-TOF as the gold standard method, the agreement was 86.7%. Regarding the antimicrobial susceptibility by disc diffusion method, all the isolates showed increased resistance against penicillin (100%), ciprofloxacin (70%), gentamicin (93.3%), tetracycline (76.6%), and clindamycin (70%). On the other hand, vancomycin and linezolid showed promising results where 100 % of the isolates were susceptible. Conclusion: We spotlight that NDC spp. is not viewed as a contaminant organism anymore, particularly in immunosuppressed patients. Timely identification, proper clinical correlation, and appropriate therapeutic intervention can lead to favorable outcomes. [ABSTRACT FROM AUTHOR]

(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population. [ABSTRACT FROM AUTHOR]

Diphtheria and tetanus could lead to serious morbidity. We aimed to evaluate immunity levels by measuring specific IgG antibodies for diphtheria and tetanus in serum samples from a nationally expanded sample of the Greek population. A geographically stratified sampling approach based on regional units (NUTS level 2) was applied by considering variables such as age group (30–80+) and sex. In total, 1201 persons (47.7% males and 52.3% females) participated in the survey. Bivariate analysis revealed a negative relationship between diphtheria and tetanus median antibody titers and age. The overall seropositivity rate for diphtheria IgG antibodies (≥0.10 IU/mL) was estimated at 31.5%. Regarding tetanus, the total seropositivity rate was estimated at 59.5% (tetanus IgG antibodies ≥0.10 IU/mL). Logistic regression analysis indicated that age groups <40 years and 40–59 years were independently associated with tetanus seropositivity. Logistic regression also revealed that male sex and being aged 60–69 years were independent risk factors for diphtheria-related seropositivity. Lastly, being resident of some regions was an independent risk factor for both diphtheria- and tetanus-related seropositivity. The present study shows that Greek adults are still not completely immune to diphtheria and tetanus. It is likely possible to achieve optimal immunization coverage by implementing serviceable public health initiatives after comprehending real community needs. [ABSTRACT FROM AUTHOR]

A seroepidemiological study was conducted in 2018 to assess diphtheria and tetanus antibodies in Guangzhou, China. Diphtheria and tetanus antibody concentrations were measured with an enzyme-linked immunosorbent assay. A total of 715 subjects were enrolled in the study. The overall diphtheria and tetanus toxoid IgG-specific antibody levels were 0.126 IU/mL (95% CI: 0.115, 0.137) and 0.210 IU/mL (95% CI: 0.185, 0.240), respectively; the overall positivity rate was 61.82% (95% CI: 58.14, 65.39) and 71.61% (95% CI: 68.3, 74.92), respectively. The diphtheria and tetanus antibody concentration was decreased by age and increased by doses. The geometric mean concentrations and positivity rate of diphtheria and tetanus antibodies were lowest and below the essential protection level in people over 14 years of age. Compared to children and adolescents, middle-aged people and the aged are at much higher risk of infection with Corynebacterium diphtheriae and Clostridium tetani. The current diphtheria and tetanus immunization schedule does not provide persistent protection after childhood. There is an urgent need to adjust the current immunization schedule. [ABSTRACT FROM AUTHOR]

A 45-year-old male presented to the emergency department (ED) with bilateral lower extremity pain, swelling, and associated atypical rash in the setting of polysubstance use and unstable housing. Laboratory tests showed an elevated white blood cell count and inflammatory markers.

Background Diphtheria is an acute bacterial infectious disease characterized by serious morbidity and mortality. Outbreaks continue to occur in developing countries despite national vaccination programs. Vaccination, early recognition the disease, and adequate intervention are needed to avoid devastating outcomes. Objective To describe the clinical spectrum of childhood diphtheria and its association to outcomes during the 2019-2020 diphtheria outberak in Yemen. Methods This was a retrospective study to assess the demographic, clinical features, and outcomes of paediatric respiratory diphtheria in patients with diphtheria during the outbreak from September 2019 until May 2020 admitted at Mukalla Maternity and Children Hospital. We used SPSS 22 version for data analysis. Results There were 34 culture-confirmed diphtheria cases included in this study, their age ranged from 13 months to 15 years old. Most of the cases (76.5%) happened to children at more than 5 years old. There was no gender difference. Of these 34-positive diphtheria, 79.4% from Hadramout and 17.6% from Shabwa governorate. Most of the cases (35.3%) were admitted in December. More than half of the patients (52.9%) were unimmunized. Fever, sore throat, and enlarged tonsils were presented in all patients, dysphagia (82.4 %), pseudomembrane (91.7%), bull neck (52.9%), and stridor (8.8%) were also found in some patients. Complications included acute renal failure (20.6%), disseminated intravascular coagulation (DIC), shock (17.6%), and myocarditis (8.8%). Significant poor outcome (P< 0.05) was associated with bull neck, myocarditis, acute renal failure, DIC, and shock. The case fatality rate (CFR) was 20.6%. Conclusion Fever, sore throat, tonsillitis, pseudomembrane, and bull neck are high index suspicion of diphtheria and anticipation of ominous outcome. The shifting of occurrence of diphtheria to older age group indicates the need for booster(s) diphtheria toxoid vaccine in addition to improving and strengthening the current immunization program.

ABSTRACTThailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p

The World Health Organization (WHO) has released its first-ever guidance on the clinical management of diphtheria. This guidance addresses the use of Diphtheria Antitoxin (DAT) and provides new recommendations on antibiotics for the treatment of diphtheria. The development of this guideline was prompted by a global increase in diphtheria outbreaks, particularly in Nigeria, Guinea, and neighboring countries. The WHO emphasizes the importance of vaccination as the primary prevention method for diphtheria, but also recognizes the lifesaving potential of antibiotics, DAT, and supportive care for patients with the disease. The full guidance can be accessed through the provided link. [Extracted from the article]

The World Health Organization (WHO) has released its first-ever guidance on the clinical management of diphtheria. This guidance addresses the use of Diphtheria Antitoxin (DAT) and provides new recommendations on antibiotics for the treatment of diphtheria. The development of this guideline was prompted by a global increase in diphtheria outbreaks, particularly in Nigeria, Guinea, and neighboring countries in 2023. The WHO emphasizes the importance of vaccination as the primary prevention method for diphtheria, but also recognizes the lifesaving potential of antibiotics, DAT, and supportive care for patients with the disease. The full guidance can be accessed through the provided link. [Extracted from the article]

Purpose To characterize the susceptibilities of positive bacterial cultures and the appropriateness of empiric antimicrobial regimens for patients admitted from post–acute care facilities (PACFs). Methods This was a retrospective quality improvement study. The study included patients admitted from a PACF to one of 2 tertiary care teaching hospitals within the University of Pennsylvania Health System, located in Philadelphia, PA, from August 2020 to December 2021. Patients were included if they had at least one positive culture within 72 hours of admission. Results A total of 167 patients and 230 isolates from the study period were evaluated. The majority of positive cultures were from a urinary source (114 of 230, 49.6%). Nineteen patients (11.4%) had a history of multidrug-resistant organisms. The most common empiric antibiotics used were vancomycin (61.7%) and cefepime (59.3%). Sixty-one patients (36.5%) received inappropriate empiric therapy based on the culture results. When comparing our hospitals' general antibiogram to that of only PACF patients, Escherichia coli and Klebsiella pneumoniae had at least a 20% difference in susceptibility to levofloxacin, ceftriaxone, and cefepime. Extended-spectrum β-lactamase resistance was also higher in the PACF cohort (odds ratio, 2.09; 95% confidence interval, 1.4-3.1). Conclusion Clinically significant differences in antimicrobial susceptibility were found among patients admitted from PACFs compared to our health system's general antibiogram. The increased resistance rates identified in this study support the need for hospitals to evaluate this at-risk patient population, which may drive changes to empiric antibiotic prescribing practices. [ABSTRACT FROM AUTHOR]

Background: Diphtheria caused by toxin‐producing Corynebacterium ulcerans is a re‐emerging human disease that can cause local and systemic sequelae. In Australia, toxigenic diphtheria is a rare notifiable communicable disease, due to high‐vaccination coverage. The public health management of cutaneous cases of toxigenic C. ulcerans varies between jurisdictions, as opposed to the more uniform public health response to toxigenic Corynebacterium diphtheriae presenting as respiratory or laryngeal diphtheria. Aim: To report a case of zoonotically acquired C. ulcerans, review evidence on the zoonotic reservoir and reported transmission events, and examine public health guidelines for the management of human and animal contacts. Methods and Results: In this case report, we detail our case investigation, treatment and public health management, including contact tracing and an approach to animal testing. We successfully identified companion canines as probable sources for the human case, with WGS confirming the link. The zoonotic disease link of C. ulcerans to domestic and agricultural animals is established in the literature; however, the management of animal contacts in human cases is inconsistent with jurisdictional or national guidelines. Conclusions: While a rare disease, a consistent approach to public health management is warranted to systematically elucidate the disease source and improve understanding of transmission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused significant disruptions in the healthcare system, affecting vaccinations and the management of diphtheria cases. As a consequence of these disruptions, numerous countries have experienced a resurgence or an increase in diphtheria cases. West Java province in Indonesia is identified as one of the high-risk areas for diphtheria, experiencing an upward trend in cases from 2021 to 2023. To analyze the situation, we developed an SIR model, which integrated DPT and booster vaccinations to determine the basic reproduction number, an essential parameter for infectious diseases. Through spatial analysis of geo-referenced data, we identified hotspots and explained diffusion in diphtheria case clusters. The calculation of Ro resulted in an Ro = 1.17, indicating the potential for a diphtheria outbreak in West Java. To control the increasing cases, one possible approach is to raise the booster vaccination coverage from the current 64.84% to 75.15%, as suggested by simulation results. Furthermore, the spatial analysis revealed that hot spot clusters were present in the western, central, and southern regions, posing a high risk not only in densely populated areas but also in rural regions. The diffusion pattern of diphtheria clusters displayed an expansion-contagious pattern. Understanding the rising trend of diphtheria cases and their geographic distribution can offer crucial insights for government and health authorities to manage the number of diphtheria cases and make informed decisions regarding the best prevention and intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Diphtheria is a contagious bacterial infection caused by Corynebacterium diphtheriae with a fatality rate of 5 - 10%. In 2020, there were about 1991 cases and 28 deaths due to diphtheria in India. Sore throats, fever, swollen glands, thick gray colored pseudo membrane over the throat are the common clinical features of Diphtheria. Environmental factors like overcrowded houses and poor socio-economic conditions lead to higher transmission of disease. Objective: To assess the clinical and laboratory profile of patients admitted in infectious disease hospital with symptoms of diphtheria. Materials and Methods: A Hospital record based cross sectional study, was carried out at an infectious disease hospital which is a tertiary care center in Hyderabad, Telangana from November 2014 to October 2015.A total of 1140 patients admitted with the symptoms and signs of Diphtheria during the period 2006 - 2010 were taken. Results: Female preponderance was noted (60.53%) and majority (24.44%) of cases were in the age group of 6 -10 years. The most common presentation was sore throat (62%), fever (60%), cough (46.3%) and dysphagia (40%). Around 2.11% patients reported myocarditis and 37.89% had positive throat swab for Klebsiella Loeffler's Bacilli. Anti-diphtheritic serum was administered to 12.8% of patients. Conclusion: Primary immunization with all 3 doses of DPT vaccine can reduce disease burden, morbidity and mortality. There is need for emphasis on effective surveillance of the disease and early detection of cases so as to promote timely initiation of treatment and prevent complications. [ABSTRACT FROM AUTHOR]

Diphtheria is a re-emerging disease with a changing epidemiology. It is thus essential to recognize diphtheria's clinical profile, patterns of morbidity and mortality, and the level of immunization. This study aimed to analyze the clinical-epidemiological profile of patients with diphtheria at the Infectious Disease Hospital, New Delhi, India. The present study was a cross-sectional investigation conducted on 94 patients diagnosed with diphtheria. The data collection tool was a questionnaire that had questions eliciting details such as socio-demographic characteristics, clinical history, examination findings, and vaccination history. The case fatality rate was calculated. Means and proportions were also measured, and the significance level was set at P <0.05. The mean±SD age of the participants was 9±4.4 years. Laryngeal involvement was found in 10 (11%) participants. Complete diphtheria vaccination doses were taken by 6 (6.4%) participants. The case fatality rate was 13%, and complications such as neuropathy were found in 21 (22%) cases, cardiac problems in 12 (13%), and respiratory problems in 13 (14%). Longer duration of the illness, delayed presentation, and complications were associated with poor clinical outcomes (P<0.05). The majority of diphtheria cases were 6-10 years old and had a low socioeconomic status. Most of them had a partial vaccination against diphtheria. Around one-third of the patients had complications related to diphtheria, and the case fatality rate was also high. Key preventive measures for controlling the deadly diphtheria disease include specialized immunization programs for areas with poor immunization coverage, as well as the early detection and treatment of suspected cases. [ABSTRACT FROM AUTHOR]

There is an unmet need for a stable and nonreactogenic vaccine against the bioterrorism agent, Coxiella burnetii, causing Q fever. Here a safe, effective, and non‐reactogenic Q fever vaccine is developed by employing self‐assembled particles (CPs) composed of cross‐reacting material 197, a nontoxic variant of diphtheria toxin. CPs are designed that incorporate selected C. burnetii antigens and assemble them inside engineered Escherichia coli at high yields. A cost‐effective manufacturing process enables the production of CP‐based Q fever vaccine candidates. Four vaccine candidates are developed, including a T‐cell epitope‐based vaccine (CP‐COX), and one that comprises two immunodominant antigens, Com1 and YbgF. The latter is tested separately (CP‐Com1, CP‐YbgF) or as a mixture (CP‐Com1/CP‐YbgF). Initial immunogenicity studies in mice reveal that the mixed CP‐Com1/YbgF elicits the highest antibody titers with a half maximal effective concentration (EC50) value of ≈100 000 and induction of TH1 and TH2 cytokines. CP‐Com1/YbgF is further evaluated in guinea pigs, demonstrating its safety and efficacy, as shown by the absence of adverse reactions and a significant reduction in febrile responses compared to alum upon challenge with C. burnetii. Together, the study shows the potential of CPs for the development of a safe and immunogenic subunit Q fever vaccine. [ABSTRACT FROM AUTHOR]

Background and aims: The World Health Organization has recently declared the frequent outbreaks of diphtheria in Nigeria as a public health concern. Although vaccination efforts have been successful in Nigeria, unfortunately, the recent 2023 outbreak in Nigeria has been nothing short of distressing. Of course, cases of diphtheria incidence are under‐reported in Nigeria. This present article aims to proffer a possible multifaceted approach to tackle outbreaks of diphtheria in Nigeria and improve immunization rates against the disease among the Nigerian population Methods: In writing this study, literature search was done about diphtheria in Nigeria using the following keywords: "diphtheria, prevalence, vaccination, efforts, challenges, and Nigeria" on PubMed, Web of Science, Google Scholar, and ResearchGate within 10 years. Result: This study found that an estimated seven million people remain unvaccinated and are at risk for infection in the country, especially people living in the Northern part of the country. Between the June 30 and August 31, 2023, Nigeria recorded an unusual increase in the number of confirmed cases of diphtheria, where a total of 5898 suspected cases were reported from 59 local government areas in 11 states across Nigeria. The majority (99.4%) of suspected cases of the disease were reported from six states: Kano (1816), Katsina (234), Yobe (158), Bauchi (79), Kaduna (45), and Borno (33). Conclusion: If Nigeria is to emerge beyond these frequent epidemics of diphtheria, the Nigerian government must work on tackling this issue on multiple fronts simultaneously, that is, at the national and international levels, as we believe that these levels would give a holistic way to unmask diphtheria in Nigeria. [ABSTRACT FROM AUTHOR]

The Asia–Pacific countries are highly diverse in health and economic conditions that may impact vaccine access and uptake. Our study aimed to characterize patterns of health access to DTP-based combination vaccines in 10 countries from 2019 to 2022 using the IQVIA-MIDAS database. The availability, affordability, and accessibility were compared across countries by national health and economic performance indicators using Spearman's rank correlation coefficient. Our findings showed that the three aspects of access to DTP-based vaccines varied substantially in the Asia–Pacific region, with higher levels in countries with better health and economic performance. Affected by the COVID-19 pandemic, vaccine accessibility fluctuates significantly in lower-income countries, with DTP coverage rates falling by more than 14% in the Philippines and Indonesia between 2019 and 2021. For availability and affordability, Singapore and Malaysia from high-income groups were largely affected, which may be related to health expenditure as a percentage of gross domestic product (Coefficient = 0.39, p = 0.03). Our study indicates that greater attention needs to be paid to national health expenditure and routine immunization services to improve vaccine disparities and increase the robustness and resilience of the vaccine supply chain during public health emergencies. [ABSTRACT FROM AUTHOR]