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The postvaccination immunity to bacterial toxins in preschool-age children with atopic dermatitis before the second revaccination has been studied. It was determined that protective immunity against Cl. tetani toxin is kept in 100% cases and against C. diphtheriae in 86,7% ones. High level of antitoxic IgG is detected in more than half of all children.

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1–55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1–5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene–bearing strains, and 3 had nontoxigenic tox gene–bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions.

In this paper, we examine the current crisis of regarding preparedness of healthcare industries in Pakistan, analyzing the causes, effects, and potential recommendations to this problem. Highlighting the efforts and issues surrounding this topic is necessary for developing and implementing research-based solutions that accurately reflect the current state of the healthcare industry. This short overview is prepared in accordance with accepted practices in published studies around the world. Our findings were based on a search of the literature databases PubMed, Google Scholar, Journals Online, and the Internet Library. Searching for "Healthcare Preparedness in Pakistan" yielded the expected results. Particularly of interest to the researchers was the question of why, despite efforts to boost vaccination rates and emergency immunization response capacities in the event of epidemics, progress on SDG3 immunization indicators has been minimal. Immunization is critically important because vaccine-preventable diseases pose a significant risk to the general population. Pakistan's authorities and government should take deliberate action to increase immunization rates. Particularly disadvantaged countries and regions are hit the worst by climate change. Pakistan continues to be hit hard by diseases like acute watery diarrhea, dengue fever, malaria, and COVID-19 are on the rise as a result of the flooding, especially in shelters and areas where water and sanitation systems have been affected. After devastating floods in KP, Sindh, and Punjab, over 70 suspected cases of diphtheria were reported. Diphtheria epidemics illustrate the precarious position of flood victims. It would be catastrophic if the newly found diphtheria strain or the covid-19 variation reached the underserved flood victims. Immunization protects against life-threatening illnesses so its government responsibility to improve immunization rates in Pakistan. [ABSTRACT FROM AUTHOR]

Diphtheria is an acute infectious disease caused by the bacterium Corynebacterium diphtheriae. Accurate and prompt diagnosis is essential for effective case management, predicting disease prognosis, preventing complications, and ensuring cost-effective medical intervention. This study aimed to assess the variety of clinical symptoms exhibited by pediatric diphtheria cases during an outbreak. An observational cross-sectional study was conducted using data from the medical records of pediatric diphtheria cases at Sulianti Saroso Infectious Disease Hospital from November 1, 2017, to February 28, 2018. The study involved 202 cases, and statistical analysis was performed using the chi-square test. Out of the 202 cases, 58.4% were male. Age distribution was 2–5 years: 24.8%, >5–12 years: 45.5%, and >12 years: 18.8%. Anamnestic findings revealed the presence of fever in 88.1% of patients, pain upon swallowing in 73.3%, and cough in 55.4%. Clinically, every patient exhibited pseudomembrane formations. Other findings included bilateral tonsillar involvement in 53%, lymphadenopathy in 40.1%, bullneck in 17.8%, and snoring in 7.9%. Four significant variables were associated with the diphtheria diagnosis: fever, snoring, bullneck, and snoring (p

A 20-month-old girl was diagnosed with Guillain – Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl’s GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.

Background: Diphtheria is a severe respiratory or cutaneous infectious disease, caused by exotoxin producing Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Diphtheria is once again prevalent due to breakdown of immunisation programmes, social disruption and unrest. Aim: This study describes the notified diphtheria cases in the Netherlands between 2000–2021 and isolates that were sent to the National Institute for Public Health and the Environment (RIVM). Methods: File investigation was performed including all notified cases and isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis that were tested for toxin production using a toxin-PCR and Elek test. An exploratory review was performed to understand transmission in populations with a high vaccination uptake. Results: Eighteen diphtheria notifications were made with confirmed toxigenic C. diphtheriae (n = 9) or ulcerans (n = 9) between 2000 and 2021. Seventeen (94.4%) presented with a cutaneous infection. All cases with a suspected source abroad (n = 8) concerned infection with C. diphtheriae. In contrast, 9/10 cases infected in the Netherlands were caused by C. ulcerans, a zoonosis. Secondary transmission was not reported. Isolates of C. ulcerans sent to the RIVM produced more often the diphtheria exotoxin (11/31; 35%) than C. diphtheriae (7/89; 7.9%). Conclusion: Both human-to-human transmission of C. diphtheriae and animal-to-human transmission of C. ulcerans rarely occurs in the Netherlands. Cases mainly present with a cutaneous infection. Travel-related cases remain a risk for transmission to populations with low vaccination coverage, highlighting the importance of immunization and diphtheria control measures. [ABSTRACT FROM AUTHOR]

Background: Luminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT). Methods: The MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzymelinked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT. Results: We identified that an equimix of WHO international standards (i.e., 06/ 142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was < 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was < 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (> 0.75) with toxin neutralization assays for PT and DT was observed. Conclusion: The MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical application effect of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) on diphtheria poisoning (DQ) .Methods A retrospective analysis was performed on 84 patients with DQ admitted to the Department of Emergency Medicine of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021.The patients were divided into the experimental group and the control group.The control group received HP,and the experimental group received HP combined with CVVH.The differences of liver and kidney function, inflammatory factors, incidence of multiple organ function injury, mortality and toxin clearance time between the two groups were compared.Results On day 7,the level of alanine aminotransferase (ALT),aspartate aminotransferase (AST),serum creatinine (Cr),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) in the experimental group were significantly decreased compared with the control group (P＜0.05),and PaO2 was significantly increased compared with the control group (P＜0.05) .There were significant differences in the clearance time of poisons in blood and urine between the two groups (P＜0.05) .Prognostic analysis showed that the incidence of MODS between the experimental group (42.2%) and the control group (69.2%) was significantly different (P＜0.05) .The mortality between the two groups was [22 (48.9%) vs.24 (61.5%) ] was not statistically significant different (P＞0.05) .Conclusion Early HP combined with CVVH can improve the clinical symptoms of patients and reduce the occurrence of multiple organ function injury, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

The pentavalent DTwP-HB-Hib (Shan-5) vaccine was first introduced into the Thailand Expanded Program on Immunization (EPI) in 2019. The Shan-5 vaccine is administered to infants at 2, 4, and 6 months of age, after initial vaccination with monovalent hepatitis B (HepB) and Bacillus Calmette-Guérin (BCG) vaccines at birth. This study compared the immunogenicity of the HepB, diphtheria, tetanus, and Bordetella pertussis antigens incorporated in the EPI Shan-5 vaccine versus the optional pentavalent (DTwP-HB-Hib) Quinvaxem and hexavalent (DTaP-HB-Hib-IPV) Infanrix-hexa vaccine. Three-dose Shan-5-vaccinated children were prospectively enrolled at the Regional Health Promotion Centre 5, Ratchaburi province, Thailand, between May 2020 and May 2021. Blood sampling was performed at months 7 and 18. The levels of HepB surface antibody (anti-HBs), anti-diphtheria toxoid (DT) IgG, anti-tetanus toxoid (TT) IgG, and anti-pertussis toxin (PT) IgG were evaluated using commercially available enzyme-linked immunoassays. Anti-HBs levels of ≥10 mIU/mL were achieved in 100 %, 99.2 %, and 99.2 % of infants in the Shan-5 EPI group, hexavalent group and Quinvaxem group one month after four dose immunization (at 0, 2, 4, 6 months of age), respectively. The geometric mean concentrations of the EPI Shan-5 and hexavalent groups were comparable but were higher than those of the Quinvaxem group. At one month after primary vaccination (month 7), infants in the Shan-5 EPI group had significantly higher levels of anti-DT IgG, anti-TT IgG, and anti-PT IgG than infants in the hexavalent and Quinvaxem groups. The immunogenicity of the HepB surface antigen in the EPI Shan-5 vaccine was similar to that achieved by the hexavalent vaccine, but was higher than that achieved by the Quinvaxem vaccine. The Shan-5 vaccine is highly immunogenic and generates robust antibody responses after primary immunization. [ABSTRACT FROM AUTHOR]

There is an ongoing resurgence of diphtheria infection worldwide despite a vaccine being available to prevent it for more than four decades. To study the clinical characteristics and risk factors for mortality of diphtheria cases among children 1–12 years of age treated in our hospital from 1 April 2014 to 31 March 2021. The data of hospitalised cases of childhood diphtheria from 1 April 2014 to 31 March 2019 were retrospectively analysed from the medical records department of our hospital. All hospitalised children with diphtheria from 1 April 2019 to 31 March 2021, were prospectively studied. All categorical variables were expressed as proportion/percentage and all continuous variables were expressed as median with interquartile range (IQR). Risk factors for morbidity and mortality were analysed and tested for significance. Unadjusted odds ratio (OR) was calculated and significant variables were subjected to multivariate logistic regression. Of the 58 children with diphtheria, 62% were lab-confirmed, most cases (45%) were between 5 and 9 years of age. Majority (57%) were completely immunised as per the national immunisation schedule. Fever (97%) was the most predominant clinical symptom. The classical diphtheria pseudo membrane was identified in all. Respiratory failure was the most predominant complication, followed by myocarditis and acute kidney injury. The case fatality rate was 8.6%. Diphtheria cases were seen among children 5–9 years of age more commonly. Infection requiring hospitalisation was seen in vaccinated children too. No atypical manifestations were observed. Complications of the disease adversely affected the overall survival. [ABSTRACT FROM AUTHOR]

Objectives: There is currently no booster diphtheria or tetanus vaccine for Lao children before adolescence, despite international recommendations. We investigated seroprotection against diphtheria and tetanus among Lao adolescents. Methods: Seven hundred seventy‐nine serum samples were tested for anti‐diphtheria and anti‐tetanus antibodies. Results: Overall, 25.8% of the adolescents had antibody titers corresponding to protection against diphtheria and 30.9% to sufficient immunity against tetanus. Female participants >16 years were more likely to be protected against diphtheria (p < 0.001) and tetanus (p < 0.029). Conclusion: Low protection against diphtheria and tetanus, possibly due to low vaccination coverage or antibody waning, suggests booster doses are warranted before adolescence. [ABSTRACT FROM AUTHOR]

A syringe for the long-term, room-temperature storage and injection of vaccines is described. Stabilisation was achieved by drying from a trehalose-containing buffer which formed an inert soluble glass distributed in the internal interconnected voids in an absorbent, compliant, reticulated, medical-grade, porous sponge. The sponge is stored inside the barrel of a syringe and the vaccines are re-solubilised by the aspiration of water. The syringe contains the sponge throughout the filling and drying processes in manufacture, and in transport, stockpiling and finally injection. The active vaccine is delivered to the patient in the normal injection process by depressing the plunger, which compresses the sponge to completely expel the dose. Full recovery of vaccine potency, after 7–10 months @ 45 °C, was shown by complete protection against supra-lethal doses of active toxins in immunised Guinea pigs. [ABSTRACT FROM AUTHOR]

Diphtheria, a vaccine-preventable disease, remains a concern in Pakistan as cases have risen post-COVID-19 pandemic causing more than 45 deaths in Pakistan in the year 2022. The respiratory variant of the disease is more common and can lead to serious complications, such as myocarditis and respiratory insufficiency. Diphtheria has caused havoc in the past killing millions of people worldwide before the development of its vaccine. Although the diphtheria toxoid vaccine is effective against toxigenic strains, there have been cases of treatment-resistant strains, particularly the non-toxigenic strains of C. diphtheriae. Pakistan's economic and health systems have suffered setbacks, which have been exacerbated by the COVID-19 pandemic. The pandemic has disrupted routine vaccination programs, and recent floods have contributed to an increase in diphtheria cases and rendered millions homeless. Poor immunization services, inadequate training of vaccination teams, and wealth inequality have all contributed to unequal vaccination coverage in Pakistan. The rising cases of diphtheria call for prompt action, including booster shots, updating vaccination records and administering immediate doses of the toxoid to close contacts. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the health and economic impact of diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) and diphtheria-tetanus-acellular pertussis vaccine (DTaP) vaccination on pertussis prevention and control in China during the 40 years from 1978 to 2017. We conducted cost-benefit analyses with a decision tree model populated with historical vaccination coverage levels and pertussis incidence and mortality data from before 1978 and during 1978 to 2017. We modeled 40 birth cohorts from birth until death. Costs and benefits were estimated from direct cost and societal perspectives (direct and indirect costs). Costs and benefits were adjusted to 2017 US dollars (USD), and future values were discounted at a 3% annual rate. We calculated net benefit values (net savings) and benefit-cost ratios of pertussis vaccination of children younger than 5 years. We conducted sensitivity analyses by varying key parameters within plausible ranges. Without DTwP and DTaP vaccination, there would be an estimated 115.76 million pertussis cases and 426 650 pertussis deaths in the 40 cohorts. With DTwP/DTaP vaccination, pertussis cases and deaths were decreased by an estimated 92.57% and 97.43%, saving 46 987.81 million USD in direct costs and 82 013.37 million USD from societal perspective. Pertussis vaccination program costs were 2168.76 million USD and 3961.28 million USD from direct cost and societal perspectives. Benefit-cost ratios were 21.67:1 from the direct cost perspective and 20.70:1 from the societal perspective. Sensitivity analyses showed the results to be robust. Over the lifetime of 40 birth cohorts, China's immunization program is preventing 93% of pertussis cases and 97% of pertussis deaths, resulting in substantial savings to the healthcare system and society. • This study aimed to evaluate the economic impact of diphtheria, tetanus, whole-cell pertussis vaccine and diphtheria-tetanus-acellular pertussis vaccine vaccination for children on the prevention of pertussis in China's 40-year immunization program. • Without the implementation of the pertussis immunization program in China, the model estimated 115.76 million pertussis cases and 426 650 deaths in the 40 newborn cohorts. • In the presence of the program, the number of cases and deaths of pertussis would decrease by 92.57% and 97.43%, respectively, and USD 46 987.81 million and USD 82 013.37 million would be averted from direct cost and societal perspective, respectively. • The benefit-cost ratios for preventing pertussis were 21.67:1 from the direct cost perspective and 20.70:1 from the societal perspective. [ABSTRACT FROM AUTHOR]

Prescribing safely for refugees and asylum seekers presents a unique set of challenges. This article discusses some of the issues that need to be addressed, including removing barriers to medicine access and ensuring continuity of care, and outlines the work of the Refugee and Asylum Seeker Service at the Alliance for Better Care. [ABSTRACT FROM AUTHOR]

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

Diphtheria is a respiratory disease caused by Corynebacterium diphtheriae. While the toxin-based vaccine has helped control outbreaks of the disease since the mid-20th century there has been an increase in cases in recent years, including systemic infections caused by non-toxigenic C. diphtheriae strains. Here we describe the first study of gene essentiality in C. diphtheriae, providing the most-dense Transposon Directed Insertion Sequencing (TraDIS) library in the phylum Actinobacteriota. This high-density library has allowed the identification of conserved genes across the genus and phylum with essential function and enabled the elucidation of essential domains within the resulting proteins including those involved in cell envelope biogenesis. Validation of these data through protein mass spectrometry identified hypothetical and uncharacterized proteins in the proteome which are also represented in the vaccine. These data are an important benchmark and useful resource for the Corynebacterium, Mycobacterium, Nocardia and Rhodococcus research community. It enables the identification of novel antimicrobial and vaccine targets and provides a basis for future studies of Actinobacterial biology. Author summary: Corynebacterium diphtheriae causes both toxin-mediated diphtheria and non-toxigenic invasive infections. Despite a vaccine to protect against diphtheria, case numbers for both invasive and diphtherial disease have increased over the last decade. Furthermore, an increase in antibiotic resistant strains are being isolated from patients. It's clear that additional treatment strategies for this organism will be needed in the future. Using high-throughput mutagenesis, this work presents the densest library of mutants for any Corynebacterium sp.. This work identifies the essential genome of C. diphtheriae; an important classification as these genes are often the target of therapeutic intervention. We identify highly conserved genes and species-specific genes unique to pathogens. This data presents an important benchmark and focus for the future development of therapeutic options. Of particular significance is the identification of uncharacterized, conserved proteins within the Diphtheria vaccine. [ABSTRACT FROM AUTHOR]

The article discusses soft tissue neck infections in children, including cervical lymphadenitis caused by viral illnesses and bacterial infections, and the appropriate antibiotic therapy for treatment.

Corynebacterium diphtheriae is responsible for both endemic and epidemic diphtheria. The predisposing factor for this disease is the failure to immunize during childhood. Humans are the only hosts of the organism and is present in the upper respiratory tract. The organism is transmitted via airborne route and can cause respiratory obstruction and heart failure because of the exotoxin it produces. There is presently a resurgence of diphtheria outbreaks in Nigeria. The Nigeria Center for Disease Control (NCDC) was notified of suspected diphtheria outbreaks in Lagos and Kano States, Nigeria, in December 2022 and has been issuing monthly reports since that time. This review of the diphtheria outbreaks following online database searches on PubMed and Google Scholar as well as the NCDC/WHO websites and grey literatures, describes the current trend of the outbreaks globally, elucidated the different strains of Corynebacterium responsible for the outbreaks, identified the recent vaccine formulation developed to tackle the outbreaks, and provide information on vaccine delivery and efficacy studies in the country and globally. [ABSTRACT FROM AUTHOR]

Purpose: Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration. Methods: Report of a case of fulminant, imported respiratory diphtheria in an otherwise healthy 24-year-old Afghan refugee in Austria in May 2022. Result: This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death. Conclusion: In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised. [ABSTRACT FROM AUTHOR]

Objective: To study the clinico-epidemiological profile and predictors of poor outcome in an outbreak of diphtheria. Methods: Records of 390 children admitted with the diagnosis of clinical diphtheria in a tertiary care teaching hospital in Nuh, Haryana, from January, 2018 to December, 2020 were analysed with respect to demographic details, immunization status, clinical features, complications and mortality. Patients were divided into survivors and non-survivors, and various variables were compared between the two groups to identify the factors associated with poor outcome. Results: Out of 390 cases, data of 318 (81.5%) was included. Young children (median age 5 year) were predominantly affected, and only 8 (2.5%) children were fully immunized. Pseudomembrane was present in 245 (77%) cases. Albert staining and culture were positive in 84.6% (269) and 12.9% (41) cases, respectively. Complications developed in 48.4% (n=154) cases and included: airway compromise 22.6% (n=72), diphtheritic cardiomyopathy 12.9% (n=41), acute kidney injury 3.7% (n=12), thrombocytopenia 8.5% (n=27) and hepatitis 0.6% (n=2) cases. Anti-diphtheritic serum (ADS) was administered to all admitted patients. Tracheostomy was done in (n=57) (17.9%) children. Case fatality rate was 17.9%. Conclusion: Diphtheria mostly affected young unvaccinated or partially vaccinated children. Mortality was high in unimmunized or partially immunized young children and those with bull neck, pseudomembrane, delayed (≥5 days) administration of ADS, acute kidney injury, thrombocytopenia and leukocytosis. Myocarditis was strongly associated with high mortality. [ABSTRACT FROM AUTHOR]

Accurate and cost-effective identification of areas where co-endemic infections occur would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots collected during cross-sectional lymphatic filariasis surveys in coastal Kenya were used for exploratory integrated detection of IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp., Ascaris lumbricoides, and Strongyloides stercoralis) as well as for detection of responses to immunizing agents used against vaccine-preventable diseases (VPDs) (measles, diphtheria, and tetanus) using a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against filarial antigens were generally higher in Ndau Island (P < 0.0001), which also had the highest prevalence of filarial antigenemia compared with other communities. Antibody responses to the Plasmodium species antigens circumsporozoite protein (CSP) and merozoite surface protein-1 (MSP-1)19 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (P < 0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against S. mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to VPDs. Seroprotection to tetanus was generally lower in Kwale County than in other counties. This study has demonstrated that MBA holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas.

Introduction: A diphtheria outbreak occurred in 2017 in Jakarta, Indonesia, during which our hospital was appointed as a referral hospital where patients with upper respiratory tract symptoms were sent for confirmation of the diagnosis and medical intervention. In this study we review the implementation of the emergency department (ED) triage process and patient flow management during the diphtheria outbreak. No previous study in Indonesia has provided a detailed report on the triage process during infectious disease outbreaks.Method: We modified our pre-existing hospital triage method according to the “identify, isolate, and inform” principle. We developed novel criteria for triage to identify triage-suspected cases and also a diphtheria package to simplify the diagnostic process. Four separate rooms were modified to isolation spaces to enable medical staff to observe these patients. We obtained data from the ED outbreak registry and electronic health records.Results: Of 60 cases of triage-suspected diphtheria, six were classified as suspected diphtheria. The mean time from “identify” to “isolate” was 3.5 minutes, and from “isolate” to “inform” was 10 minutes. Mean ED length of stay for probable diphtheria was 24.46 hours. No medical personnel in the ED showed any signs of diphtheria 30 days after the outbreak had abated.Conclusion: The modified criteria can help triage officers detect suspected diphtheria cases and measure the triage response time. Use of the diphtheria package and four separate rooms in the ED could act as an infection control procedure and facilitate the improvement of the diagnostic process.

Abstract Introduction PENTAXIM™ (Sanofi), DTaP-IPV//Hib, a pentavalent combination vaccine for protection against diphtheria, tetanus, pertussis, poliomyelitis, and invasive infections caused by Haemophilus influenzae type b, has been licensed in South Korea by the Ministry of Food and Drug Safety (MFDS) on May 9, 2016, and is currently used in routine vaccination. The aim of this phase IV study, conducted as a post-licensure commitment in South Korea, was to evaluate the safety of the DTaP-IPV//Hib vaccine when administered in infants at 2, 4, and 6 months of age in the real-world clinical practice. Methods This multicenter, observational, post-marketing surveillance (PMS) study was conducted in real-world practice in South Korea. Infants aged 2 months or older were enrolled across seven centers from July 31, 2018 to February 11, 2020. The study outcomes included occurrence, time to onset, duration, intensity, and causality assessment (for unsolicited adverse events [AEs] only) for several pre-listed solicited injection-site and systemic reactions, unsolicited AEs, and serious adverse events (SAEs). Results Data from 619 participants were included in the safety analysis. Overall, 618 AEs were reported by 273 (44.1%) participants consisting of 121 solicited injection-site reactions (15.4%), 344 solicited systemic reactions (24.6%), and 153 unsolicited AEs (15.7%) of which, 124 were unexpected AEs (12.9%) (regardless of intensity). None of the unsolicited AEs were reported to have a causal relationship with the study vaccine. One SAE of pyrexia (solicited reaction) was reported. Most AEs were of mild intensity, and all participants recovered. Conclusion This PMS study of the DTaP-IPV//Hib vaccine confirmed its safety profile in a real-life setting in South Korea and justified that the vaccine is well tolerated when used in infants aged 2 months or older for the primary series.

Vaccination, the transmission of “vaccine”, a benign disease of cows, to immunize human beings against smallpox, was invented by Jenner at the end of the eighteenth century. Pasteur, convinced that the vaccine microbe was an attenuated form of the smallpox microbe, showed that, similarly, attenuated forms of other microbes immunized against animal diseases. When applying this principle to rabies, he realized that, in this case, the vaccine was in fact composed of dead microbes. One of his students immediately exploited this result to devise a vaccine against typhoid. The vaccines against diphtheria and tetanus, in 1921, opened a new route, that of immunization with molecules from the pathogenic microbes. Molecular biology then allowed the production of the immunogenic molecules by microorganisms such as yeast, or immunization by genetically modified viruses or messenger RNA inducing our own cells to produce these molecules.

Introduction: Diphtheria is an acute disease that is transmitted through air, saliva, and direct contact with patients. In the Community Lead Total Sanitation (CLTS) targets, air quality in the house is an indicator leading to diphtheria incidence as its bacteria can spread through the air. Efforts can be made to overcome diphtheria by providing DPT-HB-HiB3 immunization to increase body immunity and enforcing the CLTS program to improve air quality. Meanwhile, East Java experienced a decrease in CLTS and DPT-HB-HiB3 coverage in 2020. This study aimed to map the distribution of the disease and describe the correlation between diphtheria and its factors. Methods: This study evaluated diphtheria incidence in 38 regencies/cities in East Java. It used the Spearman correlation test to analyze secondary data from the Health Profile of East Java in 2018-2020. Data processing was done using Health Mapper and SPSS. Results and Discussion: No correlation was found between CLTS coverage and the incidence of diphtheria in 2018 (p = 0.207; OR = 0.201) while there was a correlation between DPT-HB-HiB3 immunization coverage and the incidence of diphtheria in 2018 (p = 0.006 ; OR = 0.441). Conclusion: CLTS coverage was not associated with the incidence of diphtheria in the province rather DPT-HB-HiB3 immunization coverage was. Education for public about the importance of DPT-HB-HiB3 immunization is required and maintaining a clean environment to prevent transmission of diphtheria.

Abstract Introduction Immunosuppressive chemotherapy increase the risk of vaccine-preventable infectious diseases in children; nevertheless, chemotherapy may result in delay or miss updated immunization schedules. The predictable antibody waning after incomplete primary immunization series may be intensified at the end of chemotherapy. This study aimed to investigate post-chemotherapy vaccine immunity waning at the end of immunosuppressive therapy in children with malignancy and hematologic disorders. Materials and methods Children with malignancies and hematologic disorders including chronic immune thrombocytopenic purpura (ITP) younger than 18 years old were enrolled from September 2015 to August 2019. Eligible patients who completed their treatment protocol for at least 6 months were recruited. The patient information, including sex, age at the date of diagnosis, number of chemotherapy sessions, underlying disease, and vaccination history, was taken by chart review using predefined questionnaires. The patient’s blood samples were obtained, and serum IgG antibody titer checked against diphtheria, tetanus, hepatitis B virus (HBV), mumps, measles, and rubella (MMR) were measured by enzyme-linked immunosorbent assay (ELISA). Results 110 children receiving immunosuppressive chemotherapy were recruited. Forty-four (40%) of the children tested were girls and 66 (60%) were boys. The mean age of patients was 5.5 years with a range of 2 to 13 years. Of 110 studied children, 27.3% were seronegative for all antibodies. On average, patients undergo 19 episodes of chemotherapy. The mean chemotherapy sessions were significantly greater in children who were seronegative for all tested antibodies (mean: 36.2, 95% CI 33.16 to 39.24, p-value

Pregnant women* and their infants are at increased risk for serious influenza, pertussis, and COVID-19–related complications, including preterm birth, low-birth weight, and maternal and fetal death. The advisory committee on immunization practices recommends pregnant women receive tetanus-toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy, and influenza and COVID-19 vaccines before or during pregnancy. Vaccination coverage estimates and factors associated with maternal vaccination are measured by various surveillance systems. The objective of this report is to provide a detailed overview of the following surveillance systems that can be used to assess coverage of vaccines recommended for pregnant women: Internet panel survey, National Health Interview Survey, National Immunization Survey—Adult COVID Module, Behavioral Risk Factor Surveillance System, Pregnancy Risk Assessment Monitoring System, Vaccine Safety Datalink, and MarketScan. Influenza, Tdap, and COVID-19 vaccination coverage estimates vary by data source, and select estimates are presented. Each surveillance system differs in the population of pregnant women, time period, geographic area for which estimates can be obtained, how vaccination status is determined, and data collected regarding vaccine-related knowledge, attitudes, behaviors, and barriers. Thus, multiple systems are useful for a more complete understanding of maternal vaccination. Ongoing surveillance from the various systems to obtain vaccination coverage and information regarding disparities and barriers related to vaccination are needed to guide program and policy improvements. [ABSTRACT FROM AUTHOR]

Background and Aim: In Indonesia, diphtheria cases caused by Corynebacterium diphtheriae are still occurring. One of the causes is probably the diphtheria toxin repressor (dtxR) gene, which influences toxin expression. In this study, the gene was characterized to determine the mutations that affect the DtxR protein. Materials and Methods: The dtxR genes of 10 C. diphtheria strains isolated in Jakarta were amplified by conventional PCR. The PCR products were directed to DNA sequencing by using overlapping primers. Results & Conclusion: No mutations showed amino acid changes. We propose that the DtxR protein is conserved among bacterial strains isolated from Jakarta. [ABSTRACT FROM AUTHOR]

Background. Corynebacterium silvaticum is a pathogenic, gram-positive bacterial species that causes caseous lymphadenitis in wild boars, domestic pigs and roe deer in Western Europe. It can affect animal production and cause zoonosis. Genome analysis has suggested that one strain from Portugal and one from Austria could probably produce the diphtheria toxin (DT), which inhibits protein synthesis and can cause death. Methods. To further investigate the species genetic diversity and probable production of DT by Portuguese strains, eight isolates from this country were sequenced and compared to 38 public ones. Results. Strains from Portugal are monophyletic, nearly identical, form a unique cluster and have 27 out of 36 known Corynebacterium virulence or niche factors. All of them lack a frameshift in the tox gene and were suggested to produce DT. A phylogenetic analysis shows that the species has diverged into two clades. Clade 1 is composed of strains that were suggested to have the ability to produce DT, represented by the monophyletic strains from Portugal and strain 05-13 from Austria. Clade 2 is composed of strains unable to produce DT due to a frameshifted tox gene. The second clade is represented by strains from Austria, Germany and Switzerland. Ten genome clusters were detected, in which strains from Germany are the most diverse. Strains from Portugal belong to an exclusive cluster. The pangenome has 2,961 proteins and is nearly closed (α = 0.968). Exclusive genes shared by clusters 1 and 2, and Portuguese strains are probably not related to disease manifestation as they share the same host but could play a role in their extra-host environmental adaptation. These results show the potential of the species to cause zoonosis, possibly diphtheria. The identified clusters, exclusively shaded genes, and exclusive STs identified in Portugal could be applied in the identification and epidemiology of the species. [ABSTRACT FROM AUTHOR]

Serological surveys provide an objective biological measure of population immunity, and tetanus serological surveys can also assess vaccination coverage. We undertook a national assessment of immunity to tetanus and diphtheria among Nigerian children aged <15 years using stored specimens collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey, a national cross-sectional household-based survey. We used a validated multiplex bead assay to test for tetanus and diphtheria toxoid-antibodies. In total, 31,456 specimens were tested. Overall, 70.9% and 84.3% of children aged <15 years had at least minimal seroprotection (≥0.01 IU/mL) against tetanus and diphtheria, respectively. Seroprotection was lowest in the north west and north east zones. Factors associated with increased tetanus seroprotection included living in the southern geopolitical zones, urban residence, and higher wealth quintiles (p < 0.001). Full seroprotection (≥0.1 IU/mL) was the same for tetanus (42.2%) and diphtheria (41.7%), while long-term seroprotection (≥1 IU/mL) was 15.1% for tetanus and 6.0% for diphtheria. Full- and long-term seroprotection were higher in boys compared to girls (p < 0.001). Achieving high infant vaccination coverage by targeting specific geographic areas and socio-economic groups and introducing tetanus and diphtheria booster doses in childhood and adolescence are needed to achieve lifelong protection against tetanus and diphtheria and prevent maternal and neonatal tetanus. [ABSTRACT FROM AUTHOR]

The Public Health Agency of Sweden carried out a literature review on diphtheria vaccinations for seronegative people above 6 years of age with an uncertain vaccine history. The aim was to harmonise national Swedish recommendations with the current World Health Organization recommendations. There was no firm conclusion about dosage. Some low‐dose vaccines used in the past had suboptimal potency, while others evoked adequate levels of antitoxin after three primary doses. We concluded that low‐dose diphtheria vaccines that have been approved by a national medical products agency can be used for primary vaccination against diphtheria for individuals above 6 years of age. [ABSTRACT FROM AUTHOR]

Introduction: PENTAXIM™ (Sanofi), DTaP-IPV//Hib, a pentavalent combination vaccine for protection against diphtheria, tetanus, pertussis, poliomyelitis, and invasive infections caused by Haemophilus influenzae type b, has been licensed in South Korea by the Ministry of Food and Drug Safety (MFDS) on May 9, 2016, and is currently used in routine vaccination. The aim of this phase IV study, conducted as a post-licensure commitment in South Korea, was to evaluate the safety of the DTaP-IPV//Hib vaccine when administered in infants at 2, 4, and 6 months of age in the real-world clinical practice. Methods: This multicenter, observational, post-marketing surveillance (PMS) study was conducted in real-world practice in South Korea. Infants aged 2 months or older were enrolled across seven centers from July 31, 2018 to February 11, 2020. The study outcomes included occurrence, time to onset, duration, intensity, and causality assessment (for unsolicited adverse events [AEs] only) for several pre-listed solicited injection-site and systemic reactions, unsolicited AEs, and serious adverse events (SAEs). Results: Data from 619 participants were included in the safety analysis. Overall, 618 AEs were reported by 273 (44.1%) participants consisting of 121 solicited injection-site reactions (15.4%), 344 solicited systemic reactions (24.6%), and 153 unsolicited AEs (15.7%) of which, 124 were unexpected AEs (12.9%) (regardless of intensity). None of the unsolicited AEs were reported to have a causal relationship with the study vaccine. One SAE of pyrexia (solicited reaction) was reported. Most AEs were of mild intensity, and all participants recovered. Conclusion: This PMS study of the DTaP-IPV//Hib vaccine confirmed its safety profile in a real-life setting in South Korea and justified that the vaccine is well tolerated when used in infants aged 2 months or older for the primary series. [ABSTRACT FROM AUTHOR]

Introduction: This observational retrospective matched cohort study evaluated the safety of a prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination, Boostrix. We previously reported on the risk of maternal and neonatal outcomes; here we report on the risk of congenital anomalies in infants at birth through 6 months of age. Methods: The study included pregnant Kaiser Permanente Southern California members. Women who received the Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019 were matched to women who were pregnant between January 2012 and December 2014 and were not vaccinated with Tdap during pregnancy. Unadjusted and adjusted relative risks (aRRs) with 95% confidence intervals were estimated by Poisson regression. Quantitative secular trend analyses, from 2011 to 2017, were conducted on congenital anomalies with a statistically significant aRR > 1. Results: The analysis consisted of 16,350 and 16,088 live-born infants in the Tdap-exposed and unexposed cohorts, respectively. Of the 14 congenital anomaly body systems evaluated, 8 (eye, ear/face/neck, respiratory, upper gastrointestinal, genital, renal, musculoskeletal, integument) had statistically significant elevated aRRs, with point estimates ranging from 1.17 to 2.02. The observed elevated aRRs were consistent with their respective secular increases over time. Conclusion: Cautious interpretation of these findings is warranted as these increases may have resulted from improved identification and diagnosis. Furthermore, the biological plausibility of an association between maternal vaccine exposure in the third trimester of pregnancy and birth defects is low. The overall study findings support the safety of maternal immunization with Boostrix during the third trimester of pregnancy. Trial Registration: ClinicalTrials.gov identifier, NCT03463577. [ABSTRACT FROM AUTHOR]

• Maternal Tdap vaccination between 20 and 24 weeks of gestation is well-tolerated. • 67.5 % of pregnant women experienced ≥ 1 local reaction and 63.6 % ≥1 systemic AE. • 0.6 % of pregnant women reported mild-to-moderate fever (≥38.0˚C) post-vaccination. • Tdap vaccination between 20 and 24 vs 30-33w GA shows no increased reactogenicity. • Maternal Tdap vaccination yields no increased risks adverse pregnancy outcomes. Maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction. Pregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age. Among 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0˚C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes. Second trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns. [ABSTRACT FROM AUTHOR]