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Background: Diphtheria is an acute infectious disease caused by Corynebacterium diphtheriae. It is characterized by the formation of pseudomembranes in the tonsils, pharynx, and/or nasal cavity, which can lead to severe complications such as airway obstruction, myocarditis, and paralysis of the palate muscles. Aims: This study aims to detail the clinical course and treatment of a pediatric diphtheria case, emphasizing the importance of early diagnosis and appropriate therapeutic interventions. Methods: The case of a 5-year-old girl presenting with a 3-day history of fever at K.R.M.T Wongsonegoro Hospital is described. Clinical evaluation, including history, physical examination, and supportive tests, led to a diagnosis of diphtheritic tonsillitis. Findings: The patient exhibited classic symptoms of diphtheria, including sore throat, fever, and the presence of a dirty, greyish-white pseudomembrane on the tonsils. The membrane extended to adjacent structures, causing a condition known as bullneck. The treatment protocol included the administration of diphtheria antitoxin (DAT), antibiotics, antipyretics, corticosteroids, and symptomatic management. Conclusion: Diphtheria remains a serious infectious disease requiring prompt diagnosis and treatment to prevent complications. The case highlights the importance of early intervention, continuous monitoring, and the evaluation of therapeutic efficacy to improve patient outcomes. Implications: This study underscores the necessity of vigilant clinical practices in managing diphtheria cases, particularly in pediatric patients, to reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

The foundation story of immunology is the Christmas miracle of Emil von Behring, whose diphtheria antitoxin was first used to save the life of a child on Christmas Day 1891. Modern scholarship has dismissed it as historically and scientifically implausible: Behring's lab did not have enough antitoxin serum for use in humans, and Ernst von Bergmann had prohibited its use at the Charité. But antitoxin was tried that December by their assistants, Erich Wernicke, who processed injected rams and horses and harvested the serum for Behring, and Heinrich Geissler, who was one of Bergmann's house physicians. Especially during the Christmas season, it is easy to imagine Wernicke and Geissler bypassing protocol and giving the serum a try as a last-ditch effort to save a dying child. Derek Linton, a Behring biographer, wrote: A harried nurse confronted by a dying infant belatedly remembers that a doctor with a promising remedy for diphtheria urged her to bring hopeless cases to his attention and has him roused from his slumber on the other side of Berlin in the middle of the night on December 20, 1891. The injection of his wonder serum then rapidly resuscitates the comatose infant. Five days later, the parents celebrate the most joyous Christmas of their lives with their fully recovered daughter. [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]

Purpose: Diphtheria, still present in many countries of the world, is caused by toxigenic strains of species of the Corynebacterium diphtheriae complex, mainly Corynebacterium diphtheriae and the emerging zoonotic pathogen C. ulcerans. The immunoprecipitation test according to Elek is the gold standard for detection of the major virulence factor diphtheria toxin (DT) in toxigenic corynebacteria. Due to its sophisticated methodological requirements, the classical Elek test is performed mainly by specialized reference laboratories. It was revealed that the current modification of the Elek test does not detect the toxin in weakly toxigenic isolates. Therefore, a more robust method for detecting free DT is urgently needed, especially for toxigenic C. ulcerans strains which are known to produce often much lower amounts of DT than C. diphtheriae. Methods: Thirty-one tox-positive C. ulcerans isolates with a negative standard Elek test result previously determined as NTTB (non-toxigenic tox bearing) were re-analyzed in this study using a modified immunoprecipitation method optimized regarding different parameters including type and concentration of antitoxin, medium volume, inoculum distance from the antitoxin disk and position of controls. Results: All 31 C. ulcerans strains tested positive in the optimized Elek test. Conclusion: Only with a reliable and easy-to-handle method for detecting the toxigenicity of C. ulcerans, it is possible to assess the etiological role of this emerging zoonotic bacterium in human pathology. [ABSTRACT FROM AUTHOR]

Introduction: Diphtheria is an acute potentially fatal infectious disease caused by the toxigenic strains of Corynebacterium diphtheriae. Acute respiratory obstruction, toxic myocarditis and neurologic weakness are the most important complications of diphtheria. The clinical presentation and severity of diphtheria vary in immunised and non immunised children. Early diagnosis and prompt treatment including administration of diphtheria antitoxin and antibiotics minimise mortality. Aim: To observe the changing trends in the clinical presentation of diphtheria during the 2016 outbreak and its association with immunisation status and antitoxin administration. Materials and Methods: This longitudinal prospective study was conducted among children admitted to Government Medical College, Kozhikode, Kerala, a tertiary care centre with a diagnosis of diphtheria during January 2016 to December 2016. Details of socio-demographic data, clinical presentation, investigations, immunisation status, treatment and complications were collected using a semi-structured performa. These children were managed by an interim guideline provided by the state authorities. They were followed-up for 3 months i.e. till March 2017. The data was analysed using Statistical Package for Social Sciences (SPSS), version 18.0. Results: Among 76 children, 62(81.6%) were from Malappuram and Kozhikode districts, which have relatively low immunisation coverage. Most admissions were in July 2016. Majority 58 (76.3%) of children belonged to Muslim community. The mean age was 8.1 years with male to female ratio 1.53:1. Most of the children 47 (61.8%) were unimmunised or partially immunised. Cultures were positive for C. diphtheriae in 20 children. Complications were noted in 36 children, which included asymptomatic myocarditis in 31, symptomatic myocarditis in one, palatal palsy in nine, loss of accommodation in four and distal weakness in five. Only one child who received antitoxin within 72 hours of disease onset developed neurological complications. Complications were common in children who received less than minimum three doses of diphtheria vaccines compared to those who received three or more doses (54% vs. 44%). There was no mortality. Conclusion: There was an upward shift in age of affected children. Neurological complications were significantly less in those who received antitoxin within 72 hours of disease onset. Regular monitoring helped to detect asymptomatic myocarditis. The outbreak highlighted the need to improve awareness about diphtheria and better vaccination coverage, especially in older children. [ABSTRACT FROM AUTHOR]

Introduction: Diphtheria is an acute potentially fatal infectious disease caused by the toxigenic strains of Corynebacterium diphtheriae. Acute respiratory obstruction, toxic myocarditis and neurologic weakness are the most important complications of diphtheria. The clinical presentation and severity of diphtheria vary in immunised and non immunised children. Early diagnosis and prompt treatment including administration of diphtheria antitoxin and antibiotics minimise mortality. Aim: To observe the changing trends in the clinical presentation of diphtheria during the 2016 outbreak and its association with immunisation status and antitoxin administration. Materials and Methods: This longitudinal prospective study was conducted among children admitted to Government Medical College, Kozhikode, Kerala, a tertiary care centre with a diagnosis of diphtheria during January 2016 to December 2016. Details of socio-demographic data, clinical presentation, investigations, immunisation status, treatment and complications were collected using a semi-structured performa. These children were managed by an interim guideline provided by the state authorities. They were followed-up for 3 months i.e. till March 2017. The data was analysed using Statistical Package for Social Sciences (SPSS), version 18.0. Results: Among 76 children, 62(81.6%) were from Malappuram and Kozhikode districts, which have relatively low immunisation coverage. Most admissions were in July 2016. Majority 58 (76.3%) of children belonged to Muslim community. The mean age was 8.1 years with male to female ratio 1.53:1. Most of the children 47 (61.8%) were unimmunised or partially immunised. Cultures were positive for C. diphtheriae in 20 children. Complications were noted in 36 children, which included asymptomatic myocarditis in 31, symptomatic myocarditis in one, palatal palsy in nine, loss of accommodation in four and distal weakness in five. Only one child who received antitoxin within 72 hours of disease onset developed neurological complications. Complications were common in children who received less than minimum three doses of diphtheria vaccines compared to those who received three or more doses (54% vs. 44%). There was no mortality. Conclusion: There was an upward shift in age of affected children. Neurological complications were significantly less in those who received antitoxin within 72 hours of disease onset. Regular monitoring helped to detect asymptomatic myocarditis. The outbreak highlighted the need to improve awareness about diphtheria and better vaccination coverage, especially in older children.

Background: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks. [ABSTRACT FROM AUTHOR]

Background Respiratory diphtheria is a toxin-mediated disease caused by Corynebacterium diphtheriae. Diphtheria-like illness, clinically indistinguishable from diphtheria, is caused by Corynebacterium ulcerans , a zoonotic bacterium that can also produce diphtheria toxin. In the United States, respiratory diphtheria is nationally notifiable: specimens from suspected cases are submitted to the Centers for Disease Control and Prevention (CDC) for species and toxin confirmation, and diphtheria antitoxin (DAT) is obtained from CDC for treatment. We summarize the epidemiology of respiratory diphtheria and diphtheria-like illness and describe DAT use during 1996–2018 in the United States. Methods We described respiratory diphtheria cases reported to the National Notifiable Diseases Surveillance System (NNDSS) and C. ulcerans -related diphtheria-like illness identified through specimen submissions to CDC during 1996–2018. We reviewed DAT requests from 1997 to 2018. Results From 1996 to 2018, 14 respiratory diphtheria cases were reported to NNDSS. Among these 14 cases, 1 was toxigenic and 3 were nontoxigenic C. diphtheriae by culture and Elek, 6 were culture-negative but polymerase chain reaction (PCR)-positive for diphtheria toxin gene, 1 was culture-positive without further testing, and the remaining 3 were either not tested or tested negative. Five cases of respiratory diphtheria-like illness caused by toxigenic C. ulcerans were identified. DAT was requested by healthcare providers for 151 suspected diphtheria cases between 1997 and 2018, with an average of 11 requests per year from 1997 to 2007, and 3 per year from 2008 to 2018. Conclusions Respiratory diphtheria remains rare in the United States, and requests for DAT have declined. Incidental identification of C. ulcerans -related diphtheria-like illness suggests surveillance of this condition might be warranted. [ABSTRACT FROM AUTHOR]

Background Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment for diphtheria. The 2017–2018 outbreak among Rohingya refugees in Bangladesh was the largest in decades. We determined the outcomes of DAT-treated patients and describe the occurrence and risk factors associated with adverse reactions to DAT. Methods We conducted a retrospective study at the Médecins Sans Frontières Rubber Garden Diphtheria Treatment Center from December 2017–September 2018. Diphtheria was diagnosed based on the World Health Organization clinical case criteria. High-acuity patients were eligible for DAT. Safety precautions were meticulously maintained. We calculated the presence of adverse events by age, duration of illness, and DAT dosage using bivariate comparisons. Results We treated 709 patients with DAT; 98% (n = 696) recovered and were discharged. One-fourth (n = 170) had at least 1 adverse reaction. Common reactions included cough (n = 115, 16%), rash (n = 66, 9%), and itching (n = 37, 5%). Three percent (n = 18) had severe hypersensitivity reactions. Five patients died during their DAT infusion or soon afterwards, but no deaths were attributed to DAT. Conclusions Outcomes for DAT-treated patients were excellent; mortality was <1%. Adverse reactions occurred in one-quarter of all patients, but most reactions were mild and resolved quickly. DAT can be safely administered in a setting with basic critical care, provided there is continuous patient monitoring during the infusion, staff training on management of adverse effects, and attention to safety precautions. [ABSTRACT FROM AUTHOR]

The control of axillary bud development after removing the terminal buds (topping) of plants is a research hotspot, and the control of gene expression, like switching on and off, allows us to further study biological traits of interest, such as plant branching and fertility. In this study, a toxin gene control system for plants based on dexamethasone (DEX) induction was constructed, and the positive transgenic tobacco exhibited growth retardation in the application area (axillary bud). The expression level of the lethal Diphtheria toxin A (DTA) gene under different DEX concentrations at different application days was analyzed. The highest expression levels appeared at 5 days after the leaf injection of DEX. The DTA transcripts were induced by 5 µM DEX and peaked in response to 50 µM DEX at 5 days after leaf injection. Here, a chemical induction system, combined with a toxin gene, were used to successfully control the growth of tobacco axillary buds after topping. The DTA expression system under DEX induction was sensitive and efficient, therefore, can be used to control axillary bud growth and development in tobacco. [ABSTRACT FROM AUTHOR]

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A case of a toxigenic strain of Corynebacterium diphtheriae in an immunocompetent adult is presented, with the possibility of the adult acquiring the infection from her unvaccinated child. The abovementioned adult is a 29-year-old housewife who was previously immunised with diphtheria, tetanus, and pertussis (DTaP) vaccination in childhood, who presented fever, cough, sore throat, hoarseness of voice, odynophagia, and bilaterally enlarged tonsils. A throat swab confirmed the presence of toxigenic Corynebacterium diphtheriae. The patient was given 80,000 international units (IU) dose of diphtheria antitoxin (DAT) and treated with 2.4 million units (MU) QID intravenous penicillin and oral erythromycin 800 mg twice daily for two weeks. The patient responded well to the treatment and recovered with no cardiovascular or neurotoxicity. [ABSTRACT FROM AUTHOR]

Corynebacterium diphtheriae is a gram-positive bacillus with characteristic polar metachromatic granules. It was a significant public health problem, infecting the throat and upper airways and producing a highly potent exotoxin but with the advent of diphtheria vaccine, cases have rapidly decreased. Now over the last decade, the reemergence of this infection has been noted and case reports from India have been documented. India represents 78% of globally reported cases with significant mortality despite national immunization programs in place. This case study indicates the severity of an improperly managed case, the importance of microbiological diagnosis with a special interest in molecular detection, and reinforces a resurgence of diphtheria infection.

The article discusses a case of a 35-year-old migrant who was admitted to a hospital in Italy with pharyngeal and cutaneous diphtheria, highlighting the challenges of diagnosing and treating the condition in migrants/refugees. Topic include It also mentions the importance of contact tracing and prophylaxis following WHO guidelines for preventing the spread of the disease, which can have a high mortality rate, especially in unvaccinated individuals.

Background Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines. Methods We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST). Results We studied 267 patients (range:12−54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8−50.0%). A higher number of cases and CFR was observed among children <10 years. Mortality was associated with a delayed admission to hospital and a lack of diphtheria antitoxin. Between 2015 and 2017 there were 42 laboratory-confirmed cases. We identified 6 multilocus sequence types (STs). ST-302 was the most common (17/34, 48.6%), followed by ST67 (7/34, 20%) and ST458 (5/34, 14%). Case mapping showed a wide distribution of diphtheria patients in Metro Manila. Higher case numbers were found in densely populated areas but with no apparent clustering of ST types. Conclusions Our analysis indicates that diphtheria remains endemic in Metro Manila and that the infection is frequently fatal in young children. Improved vaccine coverage and a sustainable supply of diphtheria antitoxin should be prioritized. [ABSTRACT FROM AUTHOR]

• Manufacturing of the smallpox vaccine at the end of the 19th century was the beginning of the vaccine industry in the United States. • There is not information regarding the stocks or seed viruses used to manufacture those early vaccines. • Historical information, will allow a better understanding of the origin and evolution of the vaccine used to eradicate smallpox. For the first 80–90 years after Jenner's discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as "animal vaccine", which referred to growing vaccine material from serial propagation in calves before use in humans. The use of "animal vaccine" had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The "animal vaccine" concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of "vaccine farms" were established in the U.S. and produced large quantities of "animal vaccine". These "vaccine farms" were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The "vaccine farms" evolved from producing only smallpox "animal vaccine" to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox "animal vaccines". Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as "variants" more appropriately than "strains". Further, clonal analysis of modern "animal vaccines" indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox. [ABSTRACT FROM AUTHOR]

Introduction: The introduction of the diphtheria-tetanus-pertussis (DTP) vaccine into childhood immunization programs resulted in its widespread elimination in high-income countries. However, Nigeria is currently experiencing an outbreak. The primary cause of diphtheria outbreaks and its high mortality rates in Nigeria was waning herd immunity due to low DTP coverage and a lack of diphtheria antitoxin (DAT), respectively. However, the underlying causes of Nigeria's low DTP coverage and DAT supply remain unknown., Method: Relevant studies and reports included in our review were obtained by a search through Google Scholar, PubMed, and organization websites using the terms "Diphtheria-Pertussis-Tetanus vaccine OR Diphtheria antitoxin and Nigeria OR Diphtheria Outbreak." All articles considering diphtheria outbreaks, DTP vaccine, and DAT supply in Nigeria were considered without time restriction due to the paucity of data. We used the narrative synthesis approach to critically appraise, analyze, and draw inferences from the selected articles., Results: The main causes of low DTP coverage are insufficient supply, an inefficient cold chain system, and low uptake due to poor health literacy and negative sociocultural and religious beliefs, whereas the key barriers to DAT availability are insufficient production by pharmaceutical industries because of low demand and priority., Conclusion: The underlying causes of Nigeria's low DTP coverage and DAT supply are multifactorial. Both short-term and long-term measures are needed to control this outbreak and prevent future occurrences., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Corynebacterium diphtheriae is a gram-positive bacillus with characteristic polar metachromatic granules. It was a significant public health problem, infecting the throat and upper airways and producing a highly potent exotoxin but with the advent of diphtheria vaccine, cases have rapidly decreased. Now over the last decade, the reemergence of this infection has been noted and case reports from India have been documented. India represents 78% of globally reported cases with significant mortality despite national immunization programs in place. This case study indicates the severity of an improperly managed case, the importance of microbiological diagnosis with a special interest in molecular detection, and reinforces a resurgence of diphtheria infection. [ABSTRACT FROM AUTHOR]

Objectives: Vaccinations against diphtheria and tetanus are essential in providing immunity against these bacterial infections. The potency of diphtheria and tetanus toxoid vaccines can be measured using the in vivo toxin neutralization assay. The limit of potency of this assay was determined only for children. Therefore, we assessed the potency of adult vaccines using this assay to identify the feasibility of limit for adult vaccines. Methods: Fifteen lots of tetanus-reduced diphtheria and tetanus-diphtheria-acellular pertussis vaccines were used. In vivo toxin neutralization and lethal challenge assays were conducted on each vaccine to calculate the potencies of the toxoids. National reference standards for toxins and antitoxins were used for in vivo toxin neutralization assay. Results: All 15 lots satisfied the limits of potency for lethal challenge assay. The potency of diphtheria and tetanus toxoids exceeded 1 and 8 units/mL, respectively, for in vivo toxin neutralization assay. Conclusion: Although additional studies are required for new assays and limits, the current level of potency for adult vaccines as determined by in vivo toxin neutralization assay, was demonstrated in this study. Such efforts to improve assays are expected to promote the development of diphtheria and tetanus vaccines for adults and to contribute to vaccine self-sufficiency. [ABSTRACT FROM AUTHOR]

The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom's irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverseeffect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development. [ABSTRACT FROM AUTHOR]

The International Standard for Diphtheria Antitoxin Equine is essential for the standardisation of assays used to determine the potency of therapeutic diphtheria antitoxin products produced from equine serum. This paper describes the production and characterization of the 2nd International Standard for Diphtheria Antitoxin Equine and its calibration in International Units. Calibration was performed by toxin neutralization test in vivo and in vitro (Vero cell assay), and potency was expressed relative to the 1st International Standard to ensure continuity of the International Unit. The candidate standard (NIBSC product code 18/180) was assigned a unitage of 57 IU/ampoule based on results from 14 laboratories in 9 different countries and was established by the World Health Organisation Expert Committee on Biological Standardization in 2021. [ABSTRACT FROM AUTHOR]

Diphtheria is still a significant child health problem in countries with low immunization coverage. Reports of diphtheria in adult population are also increasing. Here we describe three recent outbreaks of diphtheria in Dibrugarh district, Assam in two consecutive years. The study was undertaken in Assam Medical College & Hospital, Dibrugarh after the diagnosis of two Diphtheria cases in the month of September and October 2015 and another in January 2016. Outbreak investigation was done after defining operational definition and throat swabs were collected from thirty three (33) individuals including three (3) index cases and thirty (30) close contacts. Diagnosis was done by clinical findings, direct microscopy, bacteriological culture and in-house designed multiplex Polymerase Chain Reaction (PCR) of the isolates for the expression of Corynebacterium diphtheriae specific rpoB gene and tox gene. Out of the 10 confirmed cases, 2 and 7 were in the first two outbreaks while only one in the third outbreak respectively. All the cases were of age > 10 years, unimmunized or partially immunized. The overall mortality was 20%. PCR results revealed all the culture positive isolates to be tox gene positive. Diphtheria is a resurgent problem in our region with a significant age shift towards adult.

Prompt administration of anti-toxin reduces mortality followingCorynebacterium diphtheriaeinfection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16–21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38–59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans. [ABSTRACT FROM PUBLISHER]

In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8% females and 62.2% males. Overall, 30.7% (95%, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1% (95%, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1% (95%, CI: 20.2-34.9) had ³ 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85%), a number of 28.5% showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.

Objective: To study the clinical profile and outcome in children with diphtheritic polyneuropathy (DP). Methodology: 13 children with polyneuropathy were included in this study. Their demographic profile, age, sex and immunization status were recorded. Detailed clinical and neurological examination was done. Investigations like CSF analysis, NCV studies, MRI brain were done. The results were tabulated and analyzed. Results: All the children presented with bulbar palsy and had h/o membranous tonsillitis. Isolated palatal palsy was seen in 7 children (53%). 6 (46.1%) children developed quadriparesis. 1 child expired and recovery is complete in rest of the 12 children. Children with isolated bulbar palsy recovered within 2 to 4 weeks while children with quadriparesis recovered within 5-6 wks. Conclusions: Any child diagnosed with diphtheria should be followed for 3-6 months in anticipation of neurological complications. DP carries good prognosis hence timely diagnosis and differentiation from other neuropathies is a prerequisite for rational management. [ABSTRACT FROM AUTHOR]