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Background: Pertussis is a highly contagious, vaccine-preventable acute respiratory infection caused by Bordetella pertussis (B. Pertussis) and affects all age groups. Since 1947, the Global Expanded Program on Immunization (EPI) was executed, and its incidence has been effectively curtailed. The reasons for the resurgence are multifactorial including the waning of vaccine acquired immunity, the difference in vaccination strategies, the adaptation of B. Pertussis strains, and an increase in disease awareness due to the strengthening of diagnostic sensitivity and surveillance sensitivity. Notably, Hewlett and Edwards proposed that the shift in pertussis transmission patterns plays an important role in pertussis resurgence. Diphtheria is an acute infectious disease of upper respiratory tract caused by toxigenic strains of Corynebacterium Diphtheriae (CD) and Corynebacterium other than diphtheriae (COD). The organism is locally invasive and causes exotoxin - mediated illness and can lead to complications like stridor, respiratory obstruction, myocarditis, nerve palsy, renal insufficiency and death in severe cases. The objective of the present study is to isolate and identify the etiological agents in clinically suspected cases of Diphtheria and Pertussis. Materials & Methods: This Prospective study has been conducted in the department of Microbiology from Feb 2022 to Aug 2024. Samples with high clinical suspicion were received and processed. Two Throat swabs were collected in patients with clinical suspicion of Diphtheria. They were inoculated on Blood agar, Potassium Tellurite agar, Tinsdale agar. Gram staining and Albert staining were done. Molecular testing also performed for C. diphtheriae. Two nasopharyngeal swabs were collected in patients with clinical suspicion of Pertussis. They were inoculated on Bordet Gengou medium, Charcoal Agar with Cephalexin and Blood Agar and Mac Conkey agar. Gram Staining was performed and Biochemical testing was carried out. Molecular testing was carried out for B. Pertussis and B. parapertussis. Results: Out of 53 samples with clinical suspicion of Diphtheriae, 6 were positive for Corynebacterium diphtheria by culture. Molecular testing was also done for testing of rpo B gene and Tox A gene. 6 samples came to be positive for C. diphtheria rpo B gene where as one was positive for tox gene production. Out of 20 cases with strong suspicion of Pertussis, culture was positive for Bordetella pertussis in 2 samples. Molecular testing came out to be positive for one sample. Testing for the antibodies by ELISA two patients were serologically positive for Pertussis. Both Culture and molecular testing was positive in one sample. Both culture and serology was positive in one sample. Only serology was positive in one sample. Conclusion: A constant surveillance is needed for vaccine preventable diseases to predict the outbreak or resurgence of cases. [ABSTRACT FROM AUTHOR]

Background: Dried blood spots (DBSs) enable the study of serological markers of various pathogens without the need to obtain serum/plasma through venipuncture. Methods: Sixty-four blood samples were prepared on Whatman™ 903 cards using specimens obtained by venipuncture to study the detection of serological markers of diphtheria, tetanus, and pertussis in DBSs, and their stability 4 months post-collection. An automated chemiluminescent immunoassay was used to investigate diphtheria, tetanus, and pertussis IgG levels from both DBSs and plasma samples. Results: An optimal cut-off value for DBSs was calculated to improve the performance of diphtheria and tetanus serological markers in DBSs, achieving high sensitivity (95% and 98%, respectively) and specificity (91.7% and 92.3%, respectively). No protection against pertussis was found in the population studied. The correlation observed between the plasma and the DBSs processed after sample collection was high (0.967–0.970) for all antibodies studied except pertussis (0.753), both considering hematocrit before sample elution or not. The correlation between DBSs and plasma for diphtheria and tetanus remained strong following a 4-month delay in DBS processing at 4 °C (0.925–0.964) and −20 °C (0.924–0.966), with only a minor decrease observed for diphtheria at room temperature (0.889), while maintaining a strong correlation for tetanus (0.960). For pertussis, the correlation between DBSs and plasma was drastically reduced after delaying its processing for 4 months at any temperature. Conclusions: To summarize, hematocrit levels within the normal range do not affect the processing of DBSs in the study of serological markers of diphtheria, tetanus, and pertussis. The DBS stability for serological diagnosis of diphtheria and tetanus is adequate when samples are stored at −20 °C for a period of 4 months. The pertussis serological marker does not appear to remain stable after 4 months, even when the DBS is stored frozen at −20 °C. [ABSTRACT FROM AUTHOR]

Background: In Yemen, diphtheria has become an important health problem since 2017 when diphtheria re-emergence as a consequence of war and the collapse of the health system. In 2023, there has been a 57% increase in diphtheria cases compared to 2021 and 2022. Damt district of Al Dhalea Governorate had the highest reported cases for year 2023. The study aims to determine the risk factors associated with diphtheria outbreak in Damt District. Methods: A retrospective matched case–control (1:2) was used. All confirmed cases based on the WHO case definition reported from Damt district during 2023 were considered cases. Two age-matched (± 5years) neighborhood controls were recruited per case. A pretested questionnaire was used for collecting data during household interviews including demographic and household characteristics, knowledge of diphtheria, vaccination status, contact with a case of diphtheria, and travel history. Frequency and proportion for quantitative and median with interquartile range (IQR) for quantitative variables. Chi-square and Mann–Whitney tests to compare the distribution of categorical and numerical variables between cases and controls. Univariate and multivariate conditional binary logistic regression, and Adjusted Odds ratio (AOR) with a 95% confidence interval at P < 0.05 were used to identify risk factors. Results: A total of 118 cases and 236 controls were enrolled, 56% were females (63% of cases vs. 53% of controls). The median (IQR) age was 14 (9,22) years for cases vs 12(7,23) of control, it was significantly higher for females than males in the case group: (16(10,29) Vs 10(6,18), P < 0.001) and control group: (15(8,25) vs 12(7,18), p-value = 0.022). Partial vaccination status AOR = 13.7(6.1–31.1), P-value < 0.001), contacts with a case of diphtheria AOR = 8.5(2.3–31.0), P value < 0.001) and Female gender, AOR = 3.3(CI; 1.1–9.5, P value = 0.029), were the main risk factors. Conclusions: Poor vaccination and contact with a case of diphtheria were the main contributors to diphtheria in the Damt district particularly among adult females. Increasing the vaccination coverage with a diphtheria-containing vaccine through routine immunization as well as tetanus-diphtheria vaccine for childbearing age females along with community awareness regarding protection measures during home care of diphtheria cases. Vaccination services as well as gender barriers related to Td vaccination should be investigated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3–6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3–6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3–6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3–6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify the factors associated with the outcome of the 2023 diphtheria outbreak in Jigawa State, Nigeria. Methods: A descriptive cross-sectional study was conducted amongst all line-listed diphtheria cases reported from Jigawa State, Nigeria, using the 2023 Integrated Disease and Surveillance Response line list of cases that met the World Health Organization case definition of diphtheria. A total of 245 line-listed cases from January 2023 to December 2023 met the criteria for inclusion in the study. Data were analysed using IBM SPSS version 22.0 with a P value set at ≤5%. Binary logistic regression was used to identify the independent predictors of the outcome of the 2023 outbreak. Results: The maximum age of the line-listed cases was 39 years, and the minimum was 1 year with a median of 8 (interquartile range = 5–8) years. More than two-thirds (68.2%) of the cases were ≥5 years of age. More than one-third of the cases (39.6%) were from the northeast senatorial zone of the state. Out of the total 245 cases, 14 died of the disease representing a case fatality rate of 6%, and an attack rate of 3.4 per 100,000 populations. The majority of the cases (95.5%) had fever, cough (81.2%), pharyngitis (86.9%), tonsillitis (96.7%) and laryngitis (82.0%). More diphtheria-related mortalities were recorded amongst cases

Abstract 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. Graphical Abstract

Abstract 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.

This study introduces a deterministic formulation for modelling the asymptotic spread of a vaccine preventable disease as well as the different stages for the progression of the disease. We derive the formula for the associated basic reproduction number. To illustrate the proposed model, we use data from the 2017–2018 diphtheria outbreak in Yemen and fit the parameters of the model. A sensitivity analysis of the basic reproduction number, with respect to the model parameters, show that this number increases with an increase of the transmission rate while this number decreases when vaccination rate increases. [ABSTRACT FROM AUTHOR]

Background Diphtheria cases continue to be reported in Indonesia, which has long been one of the countries with the highest number of diphtheria cases worldwide. One of Indonesia's province with the highest annual diphtheria cases is West Java. Dr. Hasan Sadikin General Hospital (RSHS) is one of the tertiary referral hospitals in Bandung, West Java, that treats several diphtheria cases annually. No study focused on the clinical characteristics of diphtheria cases in children admitted to RSHS between 2017 and 2021 yet. Therefore, this study sought to analyze that. Objective To find out the profiles of children < 18-year-old with diphtheria admitted in RSHS between 2017-2021. Methods This descriptive, cross-sectional study reviewed the medical records of diphtheria patients 0 to 18-year-old who were admitted to RSHS between year 2017 and 2021. Results Out of 45 subjects, 76% were males. The median of age was eight years old, ranging from 2 to 17 years. Most patients lived in urban areas and had normal anthropometry status, although some showed abnormal findings. The data showed that 44% had more than 3 days of onset until admission to the hospital, and the median length of stay was 9 days. The clinical characteristics showed that 91% of patients had pseudomembrane, also present with cough, common cold, hoarseness, stridor, and bull’s neck. As many as 44% of patients did not have complete basic immunization status. Complications found were airway obstructions, myocarditis, and sepsis, and 2 deaths were reported. Conclusion Pseudomembrane was found in the majority of patients. Most patients were over five years of age, and almost half number of the patients did not have complete basic immunization status, indicating the need for improved immunization and booster coverage.

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.

Background: Vaccine preventable diseases still account for a large proportion of childhood morbidity and mortality in children less than five of age. The decline in immunization coverage over the years has worsened this resulting in the re-emergence of hitherto controlled infections such as diphtheria. Objective: To review the presentation, management and outcome of cases of probable diphtheria seen at the children emergency centre at the Lagos University Teaching Hospital. Methods: The hospital records of all cases of suspected diphtheria adrnitted from September 2007 to September 2008 were reviewed retrospectively. The biodata, presenting complaints, duration of complaints, immunization status, management and outcome were analyzed. Results: Five cases of probable diphtheria were admitted during the study period. Two of the children died, two survived and one absconded. Three of the children had three doses each of diphtheria, pertussis and teranus (DPT) toxoid immunization but none had the 18month booster dose. Diphtheria specificantitoxin was not available for use in the management of any of the cases neither was bacteriological confirmation possible. Conclusion: Efforts to increase immunization coverage rates should be intensified and a policy to include an 18-month booster dose as part of the routine immunization in the National Programme on Immunization may be beneficial. It is recommended that diphtheria specific antitoxin be made available in the country in the event of cases with similar presentation.

Background Diphtheria cases continue to be reported in Indonesia, which has long been one of the countries with the highest number of diphtheria cases worldwide. One of Indonesia's province with the highest annual diphtheria cases is West Java. Dr. Hasan Sadikin General Hospital (RSHS) is one of the tertiary referral hospitals in Bandung, West Java, that treats several diphtheria cases annually. No study focused on the clinical characteristics of diphtheria cases in children admitted to RSHS between 2017 and 2021 yet. Therefore, this study sought to analyze that. Objective To find out the profiles of children =18-year-old with diphtheria admitted in RSHS between 2017-2021. Methods This descriptive, cross-sectional study reviewed the medical records of diphtheria patients 0 to 18-year-old who were admitted to RSHS between year 2017 and 2021. Results Out of 45 subjects, 76% were males. The median of age was eight years old, ranging from 2 to 17 years. Most patients lived in urban areas and had normal anthropometry status, although some showed abnormal findings. The data showed that 44% had more than 3 days of onset until admission to the hospital, and the median length of stay was 9 days. The clinical characteristics showed that 91% of patients had pseudomembrane, also present with cough, common cold, hoarseness, stridor, and bull's neck. As many as 44% of patients did not have complete basic immunization status. Complications found were airway obstructions, myocarditis, and sepsis, and 2 deaths were reported. Conclusion Pseudomembrane was found in the majority of patients. Most patients were over five years of age, and almost half number of the patients did not have complete basic immunization status, indicating the need for improved immunization and booster coverage. [ABSTRACT FROM AUTHOR]

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]

In South Korea, a combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) is available since 2018 for vaccination of infants from the age of 2 months. This prospective, observational, non-comparative, post-marketing study evaluated the real-world safety of DTaP-IPV/Hib primary vaccination in eligible South Korean infants from the age of 2 months between 2018 and 2022. Infants were followed up for 30 days after each vaccine dose to assess the proportion of infants experiencing any adverse event (AE), including adverse drug reactions (ADRs), unexpected AEs, and serious AEs/serious ADRs (SAEs/SADRs). Of 660 infants vaccinated during the study period, 646 were included in the total safety cohort. A total of 194 AEs were reported in 143 (22.1%) infants; 158 AEs occurred after the first dose in 130 (20.1%) infants, 21 after the second dose in 20 (13.4%) infants, and 11 after the third dose in ten (8.1%) infants. The most frequent AEs by Medical Dictionary for Regulatory Activities Preferred Terms terminology were pyrexia (13.3%), injection site swelling (5.1%), and irritability (1.7%). Most of the AEs were mild, resolved without a medical visit, and were classified as possibly related to vaccination. The incidence proportions of ADRs, unexpected AEs, and SAEs/SADRs were 19.4%, 4.3%, and 0.9%, respectively. All SAEs/SADRs resolved after hospitalization or emergency room visit, and one event was possibly related to vaccination. These results are in line with the approved label and other national/international studies, confirming the acceptable safety profile of DTaP-IPV/Hib in the South Korean pediatric population.

This research introduces a novel approach to combating diphtheria by presenting a comprehensive optimal control strategy focused on awareness campaigns to avoid direct contact with infected individuals and promote vaccinations. These campaigns highlight the severe complications of diphtheria, such as acute respiratory issues, myocarditis, and neurological paralysis. Additionally, the campaigns emphasize the negative impacts of an unbalanced lifestyle and environmental factors, as well as the importance of timely treatment and psychological support. The model aims to improve control strategies by reducing the number of infected individuals I(t) and exposed individuals E(t), as well as asymptomatic carriers A(t), which we have integrated into the model as an aspect that has been relatively unexplored in diphtheria transmission. The optimal controls are meticulously determined using Pontryagin’s maximum principle. The resulting optimality system is solved iteratively, ensuring precision and clarity in the results. Extensive numerical simulations rigorously support and confirm the theoretical analysis using MATLAB, providing concrete evidence of the strategy’s effectiveness. The broader implications and potential applications of this optimal control strategy extend to other infectious diseases, enhancing its relevance and utility in public health.

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

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.

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: 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]

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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]

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]

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]