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BACKGROUND: Despite the fact that the last cases of fully-symptomatic diphtheria were recorded in Poland in 1996 and 2000, infections caused by non-toxin-producing strains of Corynebacterium still occur. According to the epidemiological reports from ECDC in the second half of 2022, there was an increase in the number of diphtheria cases in European Union countries. As a result, the current issue becomes the appropriate preparation of microbiological laboratories for the diagnosis of Corynebacterium microorganisms. OBJECTIVE: Reidentification of diphtheria bacilli isolated from clinical samples and to assess the drug susceptibility of C. diphtheriae strains isolated in Poland. MATERIAL AND METHODS: The subject of the research were 18 strains isolated from clinical samples in Poland in 2023. Microbiological and genetic methods were used for the reidentification of the strains. Drug susceptibility was assessed using the disk diffusion method, following the new EUCAST recommendations effective from 2023. RESULTS: It was confirmed that all examined strains belonged to the genus Corynebacterium. It was de-monstrated that C. diphtheriae strains proved to be susceptible to increased exposure to benzylpenicillin and cefotaxime. Results obtained using ciprofloxacin allowed categorizing the strains into the intermediate susceptibility category WZE, except for one strain which was resistant to this antibiotic. All tested bacterial strains were susceptible to erythromycin. The C. ulcerans strain exhibited a similar antibiotic resistance profile to penicillin, cefotaxime, and ciprofloxa-cin, with additional detection of resistance to clindamycin. The toxigenicity of the tested strains was excluded. CONCLUSIONS: Based on epidemiological data regarding the emergence of new cases of infections caused by Corynebacterium strains, it is advisable to prepare theoretically and practically laboratories for diagnostics to detect potentially toxigenic diphtheria bacilli. Effective methods for the microbiological diagnosis of diphtheria bacilli are available. It is recommended to monitor the susceptibility to antimicrobial agents in all C. diphtheriae isolates.
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Antibacterianos , Corynebacterium diphtheriae , Corynebacterium , Difteria , Pruebas de Sensibilidad Microbiana , Humanos , Polonia/epidemiología , Corynebacterium diphtheriae/aislamiento & purificación , Corynebacterium diphtheriae/efectos de los fármacos , Corynebacterium diphtheriae/genética , Difteria/microbiología , Difteria/epidemiología , Corynebacterium/aislamiento & purificación , Corynebacterium/efectos de los fármacos , Corynebacterium/genética , Antibacterianos/farmacología , Infecciones por Corynebacterium/microbiología , Infecciones por Corynebacterium/epidemiología , Infecciones por Corynebacterium/tratamiento farmacológicoRESUMEN
In 2017, diphtheria outbreaks occurred in several provinces in Indonesia; however, the epidemiological data in the country is limited. The aim of this study was to determine the association between clinical findings and laboratory parameters associated with mortality of children with diphtheria. A retrospective cohort study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, covering diphtheria patients from January 2020 to December 2023. All patients aged 1-18 years clinically diagnosed with diphtheria were considered eligible. The associations between demographic characteristics, clinical features, immunization status, complications, and laboratory profiles with mortality were determined using Fisher's exact test, and the odds ratio (OR) with a 95% confidence interval (95%CI) was calculated. Our data indicated that the clinical characteristics of myocarditis (p=0.005) and airway obstruction (p=0.003) were associated with mortality. There was also a significant association between thrombocytopenia (p=0.020) and mortality in diphtheria patients. Patients with airway obstruction were 13 times more likely to have an increase in mortality compared to patients without airway obstruction. This study highlights that clinical and laboratory characteristics could be associated with in-hospital mortality of diphtheria cases, and therefore, pediatricians should be aware of the presence of those characteristics to prevent the mortality of the patients.
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Difteria , Mortalidad Hospitalaria , Humanos , Difteria/mortalidad , Difteria/epidemiología , Masculino , Femenino , Niño , Preescolar , Lactante , Estudios Transversales , Adolescente , Estudios Retrospectivos , Indonesia/epidemiología , Miocarditis/mortalidad , Miocarditis/epidemiología , Obstrucción de las Vías Aéreas/mortalidad , Obstrucción de las Vías Aéreas/epidemiología , Trombocitopenia/mortalidad , Trombocitopenia/epidemiologíaRESUMEN
Introduction Indonesia has a high incidence of diphtheria, especially in children. Surabaya has become a government regional reference center, as it is the capital of East Java province, which has the highest rate of diphtheria across the 38 regions. The aim of this study is to report our six-year pediatric diphtheria data, focusing on comparisons between before and during the pandemic era. Method This surveillance report was collected from community health centers and hospitals throughout Surabaya from January 1, 2017 to December 31, 2022. Collected data included demographic characteristics, clinical and laboratory aspects, the health centers, immunization history, and management. As per Indonesian guidelines, the diagnosis of diphtheria in this country requires a positive microbiological culture or approval from the National Experts on Diphtheria Committee. Results In total, there were 112 cases, of which 89 were found before the pandemic era. Although the number of cases declined during 2020-2022, the predominant age group, the immunization status, and the most common type of diphtheria remained consistent with pre-pandemic trends. Most cases had incomplete immunization or unimmunized children (67.8%), with the age group of 5-12 years old (44.6%), and with tonsillar diphtheria (83%). The case fatality ratio was 1.8%. Regarding the biovar of Corynebacterium diphtheriae, gravis is the most frequent finding. Conclusion The incidence of diphtheria cases in children in Surabaya was significantly lower during the pandemic. Although immunization coverage was not better, preventive measures during the pandemic may have played a role. Most patients did not have complete immunization histories during the study period, and the predominant type was tonsillar diphtheria. Since the trend in 2021-2022 increased, routine surveillance is essential.
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BACKGROUND: This case report presents an exceptionally rare and atypical presentation of diphtheria in a 17-year-old female of Hausa ethnicity residing in an area with an elevated incidence within Kano State, Nigeria. By the end of 39th epidemiological week of 2023, only two cases of cutaneous diphtheria have been reported among 5,811 cases managed at MMSH diphtheria treatment center (DTC), representing approximately 0.035% of all diphtheria cases during that time period. CASE PRESENTATION: A 17-year-old Hausa female presented with a 3-day history of throat discomfort, malaise, and muffled speech. Physical examination revealed a pseudomembrane covering the tonsillar pillars, grade 3 tonsillar enlargement, and an unusual genital manifestation characterized by extensive vulval edema, severe pain, and a large, greyish patch extending into the vaginal introitus. Her medical history was significant for recent exposure to diphtheria and the emotional impact of her sibling's death from the same disease. Diagnostic tests, including throat swab culture and histocytology, confirmed diphtheria in the throat and vulvovaginal regions. The patient was promptly initiated on diphtheria antitoxin, Azithromycin, and innovative sitz baths with hydrogen peroxide. After 4 days of Sitz bath therapy, complete pseudomembrane clearance was observed, and the patient's symptoms resolved. CONCLUSION: This case underscores the complexity of diphtheria presentations, particularly with rare pseudomembranes in both throat and vaginal regions. The successful management, combining traditional and innovative therapies, highlights the importance of recognizing and addressing unusual manifestations promptly. The potential role of auto-inoculation and the efficacy of interventions like hydrogen peroxide sitz baths warrant further investigation. Overall, this case contributes to the understanding of diverse diphtheria presentations, guiding future clinical strategies for management of diphtheria cases and emphasizing the imperative of comprehensive vaccination efforts.
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Difteria , Humanos , Femenino , Adolescente , Difteria/diagnóstico , Difteria/tratamiento farmacológico , Antitoxina Diftérica/uso terapéutico , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Nigeria , Corynebacterium diphtheriae/aislamiento & purificaciónRESUMEN
The bacterium Clostridium botulinum, well-known for producing botulinum neurotoxins, which cause the severe paralytic illness known as botulism, produces C2 toxin, a binary AB-toxin with ADP-ribosyltranferase activity. C2 toxin possesses two separate protein components, an enzymatically active A-component C2I and the binding and translocation B-component C2II. After proteolytic activation of C2II to C2IIa, the heptameric structure binds C2I and is taken up via receptor-mediated endocytosis into the target cells. Due to acidification of endosomes, the C2IIa/C2I complex undergoes conformational changes and consequently C2IIa forms a pore into the endosomal membrane and C2I can translocate into the cytoplasm, where it ADP-ribosylates G-actin, a key component of the cytoskeleton. This modification disrupts the actin cytoskeleton, resulting in the collapse of cytoskeleton and ultimately cell death. Here, we show that the serine-protease inhibitor α1-antitrypsin (α1AT) which we identified previously from a hemofiltrate library screen for PT from Bordetella pertussis is a multitoxin inhibitor. α1AT inhibits intoxication of cells with C2 toxin via inhibition of binding to cells and inhibition of enzyme activity of C2I. Moreover, diphtheria toxin and an anthrax fusion toxin are inhibited by α1AT. Since α1AT is commercially available as a drug for treatment of the α1AT deficiency, it could be repurposed for treatment of toxin-mediated diseases.
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Toxinas Bacterianas , Toxinas Botulínicas , alfa 1-Antitripsina , Toxinas Botulínicas/metabolismo , Toxinas Botulínicas/antagonistas & inhibidores , Toxinas Botulínicas/química , Humanos , alfa 1-Antitripsina/metabolismo , alfa 1-Antitripsina/química , Toxinas Bacterianas/metabolismo , Toxina Diftérica/metabolismo , Corynebacterium diphtheriae/metabolismo , Corynebacterium diphtheriae/efectos de los fármacos , Antígenos Bacterianos/metabolismo , Animales , Clostridium botulinum/metabolismo , Bacillus anthracis/metabolismo , Bacillus anthracis/efectos de los fármacosRESUMEN
BACKGROUND: Immunotoxins (ITs) represent a novel class of therapeutics with bifunctional structures that facilitate their penetration through cell membranes to induce target cell destruction. Programmed cell death ligand-1 (PD-L1), a human cell surface protein, is overexpressed in various cancers. This study aimed to construct a novel IT by genetically fusing an anti-PD-L1 Nanobody (Nb) to a truncated diphtheria toxin (DT). METHODS: The IT construct comprised a 127-amino acid anti-PD-L1 Nb fused to a 380-amino acid fragment of DT, with an N-terminal 6x-His tag. Molecular cloning techniques were employed, followed by transformation and verification through colony-PCR, enzyme digestion, and sequencing. The anti-PD-L1 Nb was expressed in WK6 E. coli cells induced by Isopropyl ß-D-1- Thiogalactopyranoside (IPTG) and purified from periplasmic extracts using immobilized Metal Ion Affinity hromatography (IMAC). The IT was similarly expressed, purified, and validated via SDS-PAGE and Western blot analysis. RESULTS: ELISA confirmed the binding activity of both Nb and IT to immobilized PD-L1 antigen, whereas truncated DT exhibited no binding. MTT assays demonstrated significant cytotoxicity of IT on A-431 cell lines compared to Nb and truncated DT controls. Statistical analyses underscored the significance of these findings. CONCLUSION: This study provides a thorough characterization of the constructed IT, highlighting its potential as a therapeutic agent targeting PD-L1-expressing cancer cells. The results support the potential of this IT in cancer immunotherapy, emphasizing the need for further investigation into its efficacy and safety profiles.
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Diphtheria is a life-threatening respiratory tract infection that causes outbreaks in susceptible populations. Between April and May 2018, an outbreak of diphtheria occurred in the eThekwini district. A school-based outbreak vaccination response was initiated to target vulnerable children and adolescents. Contribution: This study adds to the limited data describing a school-based vaccination in an outbreak response and highlights successes and challenges. School-based outbreak vaccination response can rapidly increase vaccine coverage; however, additional community engagement may be required in vaccine-hesitant populations.
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BACKGROUND: Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy. METHODS: Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI. RESULTS: By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections. CONCLUSIONS: Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts.
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Carga Global de Enfermedades , Salud Global , Humanos , Salud Global/estadística & datos numéricos , Masculino , Femenino , Adolescente , Adulto , Incidencia , Adulto Joven , Niño , Preescolar , Persona de Mediana Edad , Lactante , Anciano , Años de Vida Ajustados por Discapacidad , Recién Nacido , Anciano de 80 o más AñosRESUMEN
Vaccines containing tetanus-diphtheria antigens have been postulated to induce cross-reactive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which could protect against coronavirus disease (COVID-19). In this work, we investigated the capacity of Tetanus-diphtheria (Td) vaccine to prime existing T cell immunity to SARS-CoV-2. To that end, we first collected known SARS-CoV-2 specific CD8+ T cell epitopes targeted during the course of SARS-CoV-2 infection in humans and identified as potentially cross-reactive with Td vaccine those sharing similarity with tetanus-diphtheria vaccine antigens, as judged by Levenshtein edit distances (≤ 20% edits per epitope sequence). As a result, we selected 25 potentially cross-reactive SARS-CoV-2 specific CD8+ T cell epitopes with high population coverage that were assembled into a synthetic peptide pool (TDX pool). Using peripheral blood mononuclear cells, we first determined by intracellular IFNγ staining assays existing CD8+ T cell recall responses to the TDX pool and to other peptide pools, including overlapping peptide pools covering SARS-CoV-2 Spike protein and Nucleocapsid phosphoprotein (NP). In the studied subjects, CD8+ T cell recall responses to Spike and TDX peptide pools were dominant and comparable, while recall responses to NP peptide pool were less frequent and weaker. Subsequently, we studied responses to the same peptides using antigen-inexperienced naive T cells primed/stimulated in vitro with Td vaccine. Priming stimulations were carried out by co-culturing naive T cells with autologous irradiated peripheral mononuclear cells in the presence of Td vaccine, IL-2, IL-7 and IL-15. Interestingly, naive CD8+ T cells stimulated/primed with Td vaccine responded strongly and specifically to the TDX pool, not to other SARS-CoV-2 peptide pools. Finally, we show that Td-immunization of C57BL/6J mice elicited T cells cross-reactive with the TDX pool. Collectively, our findings support that tetanus-diphtheria vaccines can prime SARS-CoV-2 cross-reactive T cells and likely contribute to shape the T cell responses to the virus.
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Linfocitos T CD8-positivos , COVID-19 , Reacciones Cruzadas , Epítopos de Linfocito T , SARS-CoV-2 , Humanos , Reacciones Cruzadas/inmunología , SARS-CoV-2/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Toxoide Tetánico/inmunología , Animales , Ratones , Femenino , Vacunas contra la COVID-19/inmunología , Masculino , Adulto , Glicoproteína de la Espiga del Coronavirus/inmunología , Persona de Mediana EdadRESUMEN
Abstract: Diphtheria is a potentially fatal bacterial infection caused by toxin-producing strains of corynebacteria, most often Corynebacterium diphtheriae and less commonly Corynebacterium ulcerans. Incidence of the disease has fallen significantly since the introduction of vaccination programs; it is now rare in countries with high vaccination coverage such as Australia. This article presents the most recent respiratory cases of diphtheria in two children in New South Wales-the first locally acquired childhood cases in Australia in 30 years-and discusses potential contributing factors. These encompass the lack of clinical awareness and the delays in laboratory diagnosis in regional laboratories. The cases also highlight the problem of vaccine hesitancy and the role that primary carers play in addressing these anxieties. While clinical management of the cases progressed well, factors in the public health responses were complicated by access to appropriate care and by delays in antibiotic sensitivity profiles. The public health response to these cases raises important considerations for clinicians and public health practitioners, including preparedness for rare and re-emerging diseases, the need for culturally safe environments and the importance of addressing vaccine hesitancy. Preparedness requires consideration of the capacity of regional health systems with fewer resources and of how public health departments can support response to multiple crises. Preparedness also relies on access to necessary diagnostic laboratory resources, on up-to-date guidelines, and on maintaining awareness among clinicians for these rare infections.
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Difteria , Humanos , Difteria/epidemiología , Difteria/prevención & control , Masculino , Nueva Gales del Sur/epidemiología , Femenino , Corynebacterium diphtheriae , Preescolar , Niño , Vacunación , Australia/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Antibacterianos/uso terapéuticoRESUMEN
We describe a case of a 40-year-old South Asian woman who presented with symptoms suggestive of postural orthostatic tachycardia syndrome (POTS) following a diphtheria toxoid and tetanus toxoid (dTdap) booster vaccination administered one week prior. The patient's POTS responded favorably to treatment with low-dose fludrocortisone and ivabradine. Clinicians should maintain a high index of suspicion for POTS as a possible vaccine adverse event (VAE) post-dTdap booster inoculation and be aware of appropriate management strategies.
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CRM197EK is a derivative of diphtheria toxoid cross-reactive material-197 (CRM197) with two-point mutations (K51E and E148K) to improve its properties for a vaccine conjugate and drug delivery. A previous study has shown that intracellularly expressing CRM197EK in Escherichia coli (E. coli) host formed inclusion bodies that need a complicated purification and refolding step. Protein purification from inclusion bodies can be overcome by solubilization of inclusion bodies by using N-lauroyl sarcosine (sarkosyl). In this work, recombinant CRM197EK (rCRM197EK) was expressed in E. coli BL21 (DE3) as inclusion bodies, then solubilized using sarkosyl to form a soluble rCRM197EK without the need for a renaturation process. Furthermore, rCRM197EK was purified using the Ni-NTA column, characterized by SDS-PAGE and Western Blot, and its biological activity was assayed through its DNase activity. Moreover, its binding affinity with anti-diphtheria toxin (DT) antibody was measured using the surface plasmon resonance (SPR). The result showed that solubilization with sarkosyl form soluble rCRM197EK (61.61 kDa) was confirmed by SDS-PAGE and Western Blot with a yield of 2.8 mg/mL. rCRM197EK shows DNase activity, and the SPR assay shows that it can interact with an anti-DT antibody with a binding energy of - 9.2 kcal/mol.
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The use of the serum or plasma of patients or animals who have recovered from an infectious disease, or had been immunized with a relevant antigen, to treat or prevent the same infection in others began in the late 1880s when French and German scientists uncovered, one step at a time, several of the elements of the immune system's response to infection. A key finding was that the damage caused by some bacteria depends upon their secreted toxins which can be neutralized by biologic agents. Antitoxins to diphtheria and tetanus began to be manufactured in large animals in France, Germany, and the US in the 1890s and were soon being used worldwide. The impact of diphtheria antitoxin on childhood mortality was profound. Shortly after the development of antitoxins, convalescent serum began to be used for its anti-bactericidal properties thus addressing serious infections caused by non-toxin-producing organisms. The effectiveness of antitoxins and antisera was demonstrated by examining mortality rates in hospitals before and after the introduction of antitoxins, by comparisons of treated and untreated patients, by comparing early and late treatment and dosage, by examining vital data mortality trends, and by several randomized and alternate assignment trials. Antitoxins continue to have a role in the rare cases of diphtheria and other conditions largely eradicated by immunization, but serum therapy nearly disappeared from the medical armamentarium with the development of antibiotics in the 1940s. Inasmuch as new human pathogens are now emerging with unprecedented regularity as seen in the recent COVID-19 pandemic, and because specific therapies are unlikely to be available for them, plasma-based antibody therapies are likely to again carve out a niche in infectious disease control.
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OBJECTIVES: From September 2022 an increase in Corynebacterium diphtheriae (C. diphtheriae) infections was reported in Europe. Our study focuses on 31 adolescent and young adult refugees with cutaneous C. diphtheriae infections detected in Germany. We examined treatment regimens and outcomes to provide targeted insights into the management of this infection. METHODS: We distributed a standardized survey, focused on children and adolescents presenting to paediatric clinics through the German Paediatric Infectious Diseases Society (DGPI) and additional professional contacts in Germany. Data were extracted from routine medical documentation and reported anonymously. RESULTS: A total of 31 individuals with cutaneous C. diphtheriae infection were reported by 9 centres. Two of these showed diphtheria toxin (DT) related systemic symptoms and four exhibited systemic inflammation requiring complex management. The remaining 25 cases, with exclusively cutaneous manifestations, were afebrile. Treatment with topical antiseptics and systemic antibiotics, mainly aminopenicillin/beta-lactamase inhibitors (BLI) (35%) or clindamycin (25%), achieved eradication in all but two cases treated with aminopenicillin/BLI. Treatment duration varied between 5 and 17 days. CONCLUSIONS: In refugees presenting with chronic skin wounds, C. diphtheriae should be included into the differential diagnosis. Fever seems to be a valuable marker to differentiate severe cases with potentially DT-mediated sequelae from exclusively cutaneous diphtheria (CD). For afebrile CD, topical antiseptics and oral antibiotic therapy with clindamycin for 7 days, followed by clinical surveillance appears to be a safe treatment regimen. Patients with CD who present with fever or pharyngitis should be thoroughly investigated including blood and pharyngeal swab cultures.
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Targeted intracellular delivery of therapeutic proteins remains a significant unmet challenge in biotechnology. A promising approach is to leverage the intrinsic capabilities of bacterial toxins like diphtheria toxin (DT) to deliver a potent cytotoxic enzyme into cells with an associated membrane translocation moiety. Despite showing promising clinical efficacy, widespread deployment of DT-based therapeutics is complicated by the prevalence of pre-existing antibodies in the general population arising from childhood DT toxoid vaccinations, which impact the exposure, efficacy, and safety of these potent molecules. Here, we describe the discovery and characterization of a distant DT homolog from the ancient reptile pathogen Austwickia chelonae that we have dubbed chelona toxin (ACT). We show that ACT is comparable to DT structure and function in all respects except that it is not recognized by pre-existing anti-DT antibodies circulating in human sera. Furthermore, we demonstrate that ACT delivers heterologous therapeutic cargos into target cells more efficiently than DT. Our findings highlight ACT as a promising new chassis for building next-generation immunotoxins and targeted delivery platforms with improved pharmacokinetic and pharmacodynamic properties.
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BACKGROUND: In recent years, notified pertussis cases have been increasingly documented in China. It raised a new public health concern of potential optimization in immunization strategy. This study was aimed to determine the cost-effectiveness of different immunization strategies against pertussis-containing vaccines for 6-year-old pre-school children in Shanghai. METHODS: A Markov-decision tree model was applied to evaluate two pertussis immunization strategies for 6-year-old pre-school children as following: (1) 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster vaccinated at 6 years of age, and (2) no booster at 6 years of age regimen. Primary outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-utility ratios (ICUR). Sensitivity analyses were performed. The analysis was conducted over a study period of 14 years from a societal perspective. RESULTS: Compared to no booster immunization strategy, administering 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster at 6 years of age, resulted in an average cost reduction of CNY 814.16 (USD 116) per individual, an increase in QALYs by 0.00066, and a rise in per capita net monetary benefit (NMB) by CNY 933.51 (USD 132). The total costs over the study period were reduced by CNY 160.59 million (USD 23 million), utility increased by 130.49 QALYs, and NMB increased by CNY 184.14 million (USD 26 million). CONCLUSIONS: Implementing acellular pertussis booster immunization for 6-year-old pre-school children in Shanghai emerges as a cost-saving immunization strategy, with both cost savings and utility gains.
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Análisis de Costo-Efectividad , Inmunización Secundaria , Años de Vida Ajustados por Calidad de Vida , Tos Ferina , Niño , Femenino , Humanos , Masculino , China/epidemiología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/economía , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Inmunización Secundaria/economía , Cadenas de Markov , Vacuna contra la Tos Ferina/economía , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacunación/economía , Vacunación/métodos , Tos Ferina/prevención & control , Tos Ferina/economíaRESUMEN
A case of severe respiratory diphtheria complicated by myocarditis is reported. Diphtheria myocarditis manifested as cardiogenic shock and progressive conduction disturbance. Temporary transvenous ventricular pacing was used to manage this complication successfully. However, this patient died from cardiogenic shock. This case highlights that sporadic cases of diphtheria still occur despite high vaccination rates in Saudi Arabia. Conduction abnormalities in diphtheria myocarditis carry a prognostic marker for the severity of cardiac injury.
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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.
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Corynebacterium diphtheriae , Difteria , Humanos , Guyana Francesa/epidemiología , Estudios Retrospectivos , Femenino , Masculino , Corynebacterium diphtheriae/aislamiento & purificación , Corynebacterium diphtheriae/genética , Adulto , Persona de Mediana Edad , Adolescente , Niño , Adulto Joven , Preescolar , Difteria/epidemiología , Difteria/microbiología , Anciano , Incidencia , Lactante , Historia del Siglo XXI , Infecciones por Corynebacterium/epidemiología , Infecciones por Corynebacterium/microbiologíaRESUMEN
BACKGROUND: Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated. METHODS: The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays. RESULTS: TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells. CONCLUSION: The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.