Diphtheria In Patients Research Articles

Humoral Immunity and Antibody Responses against Diphtheria, Tetanus, and Pneumococcus after Immune Effector Cell Therapies: A Prospective Study.

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.

Clinical spectrum and outcomes of the 2019-2020 pediatric diphtheria outbreak in Yemen

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

PA01 Crusted nodules in returning travellers

Abstract We present the cases of two brothers, aged 10 and 13 years, who, on returning from a 6-week holiday in Sri Lanka, presented to the emergency department with painful, pruritic crusted nodules. Both children were usually fit and well, and up to date with their childhood immunizations; the older brother had a background of mild eczema. On examination, there were multiple widespread 1–2 cm well-defined, superficial excoriated ulcers with overhanding crusted edges. These were present over the arms, legs, back and feet of the younger brother, and the lower legs and feet of the older brother. There was no history of prodromal illness, and they remained afebrile throughout, with no evidence of lymphadenopathy or systemic illness. Bacterial wound swabs demonstrated Corynebacterium diphtheriae. Real-time polymerase chain reaction confirmed the presence of TOX, followed by the Elek test, which demonstrated the expression of the diphtheria toxin, confirming the diagnosis of cutaneous diphtheria due to a toxigenic strain. Both children were treated empirically with intravenous flucloxacillin and clindamycin as inpatients. Both were clinically well and discharged home on oral clindamycin and co-amoxiclav for a total of 10 further days. Public Health was informed of this notifiable disease, with contact tracing and appropriate family screening performed. Our patients isolated appropriately and made a full recovery, with negative swabs. Historically, most cases of diphtheria have been caused by C. diphtheriae (a Gram-positive nonencapsulated, nonsporulating, nonmotile bacillus) with an incubation period of 2–7 days, although other strains, notably Corynebacterium ulcerans, become increasingly prevalent. Despite diphtheria being classically described as a respiratory illness, Public Health England data found that nearly two-thirds of toxigenic C. diphtheriae infections were cutaneous in presentation. Concurrent respiratory infection and cutaneous infection are rare. Either form can be caused by toxigenic or nontoxigenic strains; the former may result in toxic complications (such as myocarditis, polyneuritis, septic arthritis, osteomyelitis and death); however, these are rare in cutaneous diphtheria, even if TOX-positive. Systems review of our patients did not highlight any of these features in our patients. Our patients exemplify classic features of cutaneous diphtheria and raise an important reminder to consider diphtheria in patients returning from endemic areas, despite vaccination schedules being in place.

Genetic characterization of diphtheria tox B to evaluate vaccine efficacy in Indonesia.

Blocking the attachment of diphtheria toxins to host cells through the intact receptor binding site (tox B) was the initial mechanism of action of the diphtheria vaccine. Diphtheria outbreaks in populations with good vaccination coverage can be caused by mutations or changes in the genetic structure of the tox B protein. The aim of this study was to characterize the Tox B protein produced by Corynebacterium diphtheriae isolated from 2018 to 2019 in patients in Jakarta who had already received the diphtheria vaccine. Of the 89 throat swab specimens of patients with a clinical diagnosis of diphtheria, 10 were positive for diphtheria and toxin. PCR was used to amplify the tox B DNA fragment in the 10 positive isolates. DNA sequencing was conducted with overlapping primers and the DNA sequences were analysed by using SeqScape V2.7. Of the 10 isolates, nine isolate showed a DNA mutation (G30A), but the mutation did not change the amino acid encoding arginin (silent mutation). Our findings indicate that the efficacy of the diphtheria vaccine used in Indonesia has not decreased because of mutations in the tox B genes not change the amino acid. Overall, there are no amino acid changes in the tox B protein, indicating that the outbreaks are not affected by mutation in tox B. Another possible mechanism - overexpression of the toxin - is likely responsible for causing diphtheria in patients who have a complete history of immunization in Indonesia.

Safety of antibodies to measles, mumps, rubella and diphtheria in patients with juvenile idiopathic arthritis

Introduction. The issue of protection against vaccinepreventable diseases has acquired new urgency in connection with the decrease in the vaccination rate established by WHO against the background of the COVID-19 pandemic. This creates the conditions for outbreaks and puts patients with immunopathological diseases at particular risk, who are most often not vaccinated from the moment of diagnosis Purpose of the study – to assess the safety of specific antibodies to measles, mumps, rubella and diphtheria in children with JIA, depending on the duration of vaccination, the duration of the disease and the therapy received.Materials and methods. The vaccination rate of 171 children with juvenile idiopathic arthritis (JIA) aged (11,31±0,31 years) with the duration of the disease at the time of examination was 4,69±0,29 years, who had previously received 1-2 vaccinations against measles, mumps, rubella and 3-6 vaccinations against diphtheria. Antibodies to these infections were determined by ELISA.Results. 42.1% of children had no protective titers of antibodies to measles, 19,9% – to mumps, 9,4% – to rubella and 16,4% – to diphtheria. Among 93 vaccinated and revaccinated patients, there were no protective titers of antibodies to measles – 40,9% (38 children), mumps – 13,9% (13 people), rubella – 5,4% (5 children), and among 78 vaccinated once, respectively: measles – 43.6% (34 children), mumps – 25.6% (20 children), rubella – 14,1% (11). The level of protection against diphtheria was comparable for those who received 3-5 vaccinations. Depending on the therapy, 3 groups were identified: group 1-71 children received metatrexate and glucocorticosteroids, 2-82 children received modifying anti-rheumatic drugs (DMARD) and 18 children without this therapy (Group 3). Children of the 2nd group were on average older (12,48±0,42 years) than in the 1st and 3rd groups (10,04±0,48 and 10,96±0,96 years, respectively), they had significantly more frequent systemic variant and polyarthritis (64,6% compared to 36,6% and 16,7%, px2<0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. >˂0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. The average level of antibodies to measles in children of group 2 (0,32±0,07 IU/ml) was 2,8 times less than in group 3 and significantly less than in group 1 (0,78±0,16, Pt=0.009), the average value of antibodies to rubella was also significantly less in group 2 (84,48±7,34 IU/ml) than in group 1 (109,73±8,09, Pt=0,022) and in group 3 (120,01±15,42, Pt=0,042). The analysis showed that the safety of antibodies to antigens of live vaccines, especially against measles, is negatively affected by the duration of the disease and the nature of therapy. Children who received combined therapy with anti-TNF, anti-IL-6 and anti-CD-80 drugs had a longer duration of the disease (7,5±0,97 years)=0,00082 compared to those who received only anti-IL-6 (2,9±0,7 years) and antiTNF therapy (6,1±0,5 years) and with a comparable number of vaccine doses received, significantly lower average values of antibodies and a larger number of unprotected ones.Conclusions. The duration of the disease, the lack of timely age-related revaccinations, as well as the presence of combination therapy aimed at suppressing various mechanisms of the immune response in children with JIA are factors that lead to an increase in the number of unprotected from controlled infections. Immunity to measles suffers the most – 40.9% of revaccinated people are unprotected.

Preservation of Postvaccinal Immunity to Measles, Rubella, Parotitis, Hepatitis B and Diphtheria in Patients With Juvenile Idiopathic Arthritis Who Undergone Planned Immunization Under the Age of Two: Preliminary Results of Cross-Sectional Study

Background. Patients with juvenile idiopathic arthritis (JIA) can have low levels of antibodies to vaccine antigens due to immunologic features of the main disease, disruptions in vaccination schedule and immunosuppressive drugs administration Objective. The aim of the study was to examine the status of postvaccinal immunity and determine the factors associated with preservation of protective level of antibodies in patients with JIA. Methods. This cross-sectional study included patients with JIA at the age from 2 to 17 years old vaccinated under the age of two (before JIA) against measles, rubella, parotitis, hepatitis B and diphtheria. Levels of IgG to vaccine antigens were measured by enzyme immunoassay. The minimum protective level of anti-measles IgG was esteemed as 0.18 IU/ml, antibodies to rubella — 10 IU/ml, for parotitis — COI > 1.0, for hepatitis B — 10 mIU/ml, antibodies to diphtheria — 0.09 IU/ml. Results. The study included 90 patients with JIA (71% of girls) at the age (median) 11.3 (7.5; 14.9) years. The age of JIA manifestation was 6.0 (4.0; 8.0) years, disease duration — 4.0 (2.0; 7.3) years. Glucocorticosteroids administration in anamnesis or at study entry was recorded in 24/88 (27%) patients, methotrexate — 81/88 (92%), genetically engineered biologic drugs — 54/89 (61%). Protective level of antibodies to measles virus was revealed in 45 (50%) children with JIA, to rubella virus — in 88 (98%), to parotitis — in 68 (76%), to hepatitis B — in 49 (54%), to diphtherial anatoxin — in 45 (50%). The decrease of postvaccinal immunity level was associated with JIA duration and glucocorticosteroids administration (against diphtheria) duration, as well as drop-out immunization (against measles). Conclusion. Major part of children with JIA have no protection against measles, parotitis, hepatitis B or diphtheria. High risk of progression of such vaccine-preventable diseases in these children demands development of individual programs of immunization.

Genomic analysis of endemic clones of toxigenic and non-toxigenic Corynebacterium diphtheriae in Belarus during and after the major epidemic in 1990s

BackgroundDiphtheria remains a major public health concern with multiple recent outbreaks around the world. Moreover, invasive non-toxigenic strains have emerged globally causing severe infections. A diphtheria epidemic in the former Soviet Union in the 1990s resulted in ~5000 deaths. In this study, we analysed the genome sequences of a collection of 93 C. diphtheriae strains collected during and after this outbreak (1996 – 2014) in a former Soviet State, Belarus to understand the evolutionary dynamics and virulence capacities of these strains.ResultsC. diphtheriae strains from Belarus belong to ten sequence types (STs). Two major clones, non-toxigenic ST5 and toxigenic ST8, encompassed 76% of the isolates that are associated with sore throat and diphtheria in patients, respectively. Core genomic diversity is limited within outbreak-associated ST8 with relatively higher mutation rates (8.9 × 10−7 substitutions per strain per year) than ST5 (5.6 × 10−7 substitutions per strain per year) where most of the diversity was introduced by recombination. A variation in the virulence gene repertoire including the presence of tox gene is likely responsible for pathogenic differences between different strains. However, strains with similar virulence potential can cause disease in some individuals and remain asymptomatic in others. Eight synonymous single nucleotide polymorphisms were observed between the tox genes of the vaccine strain PW8 and other toxigenic strains of ST8, ST25, ST28, ST41 and non-toxigenic tox gene-bearing (NTTB) ST40 strains. A single nucleotide deletion at position 52 in the tox gene resulted in the frameshift in ST40 isolates, converting them into NTTB strains.ConclusionsNon-toxigenic C. diphtheriae ST5 and toxigenic ST8 strains have been endemic in Belarus both during and after the epidemic in 1990s. A high vaccine coverage has effectively controlled diphtheria in Belarus; however, non-toxigenic strains continue to circulate in the population. Recombination is an important evolutionary force in shaping the genomic diversity in C. diphtheriae. However, the relative role of recombination and mutations in diversification varies between different clones.

Immunogenicity and Clinical Efficacy Combined Vaccine against Diphtheria, Tetanus and Hepatitis B in Patients with Chronic Obstructive Pulmonary Disease

The article presents the results of vaccination against diphtheria, tetanus and hepatitis B virus with the use of combined vaccine Bubo-M or a monovalent vaccine Hepatitis B in 120 patients with severe and medium chronic obstructive pulmonary disease (COPD) and 77 healthy people at the age 35 - 60 years. The lack of protective antibodies to diphtheria in patients with COPD was noted. The safety of immunization and the delayed production of post-vaccination antibodies to these infections were shown. The level of post-vaccination antibodies was the same as in healthy group after the administration of 3-rd dose both of the monovaccine and the combined one. During the year a clinical effect in reducing the number of exacerbations of the disease after a triple injection of the combined Bubo-M vaccine in patients with COPD was observed, comparable to that in patients with the combined use of the immunomodulator and hepatitis B vaccine. Moreover combined vaccination with immunomodulator led to normalization of level of the inflammatory mediators. Conclusion: Vaccination of patients with COPD with the use of the combined vaccine Bubo-M has both an advantages in clinical effect and the spectrum of anti-infection protection in comparison with the monovaccine against hepatitis

A 5-year follow-up on antibody response after diphtheria and tetanus vaccination in hemodialysis patients

Chronic renal failure is associated with a T-cell-dependent immune defect. In the past, various studies have focused on the insufficient immune response to vaccination of hemodialysis patients. An impaired vaccination response rate has been reported for vaccines against hepatitis B, influenza, tetanus, diphtheria, and others. However, no data exist on the long-term success of vaccination against tetanus and diphtheria in these patients. The aim of the present study is to investigate seroresponse to tetanus and diphtheria vaccination over a 5-year period. Antibody levels were determined by enzyme immunoassay. Antidiphtheria antibody levels of 31 hemodialysis patients were determined 5 years after vaccination. After 5 years, 10 of 31 patients (32%) had a protective antibody level against diphtheria (≥0.1 IU/mL), whereas 12 months after vaccination, 26 of 71 patients (37%) were protected. Also, mean antibody levels significantly decreased. Furthermore, antitetanus antibody levels of 21 patients simultaneously vaccinated against tetanus and diphtheria were investigated. After 5 years, 15 of 21 patients (71%) were protected compared with 46 of 71 patients (65%) in the hemodialysis collective studied after 12 months. In the interval between 1 and 5 years after vaccination, significantly more patients in the initial nonresponder group had died than in the responder group; therefore, the overall protection rate observed in vaccinated patients increased. Our results provide evidence that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid. Therefore, detection of individual antibody concentrations may be indicated to decide on revaccination. © 2001 by the National Kidney Foundation, Inc.

Diphtheria as a model. Introduction of serums and vaccines for scarlet fever and pneumococcal pneumonia.

Although the investigations of Pasteur and Koch opened a new world to the scientists of their day, in the beginning they contributed nothing to the therapy of disease. The first clear-cut demonstration that the science of bacteriology could lead to the cure of disease came when Behring announced, in 1890, that the serum of animals immunized with diphtheria toxin protected other animals against infection with the diphtheria bacillus. 1 A year later clinicians began to use this antiserum to check the course of diphtheria in patients. 2(p261) Research on diphtheria took a second practical step forward when Behring showed in 1913 that the toxin could be used to immunize humans against the disease. 3 Thus, the pattern was laid down for others to follow: Find a toxin for each bacterium being investigated, use it to immunize animals and humans against the disease, and obtain an antiserum from animals that will

Diphtheria as a Model

Although the investigations of Pasteur and Koch opened a new world to the scientists of their day, in the beginning they contributed nothing to the therapy of disease. The first clear-cut demonstration that the science of bacteriology could lead to the cure of disease came when Behring announced, in 1890, that the serum of animals immunized with diphtheria toxin protected other animals against infection with the diphtheria bacillus.¹A year later clinicians began to use this antiserum to check the course of diphtheria in patients.^2(p261)Research on diphtheria took a second practical step forward when Behring showed in 1913 that the toxin could be used to immunize humans against the disease.³ Thus, the pattern was laid down for others to follow: Find a toxin for each bacterium being investigated, use it to immunize animals and humans against the disease, and obtain an antiserum from animals that will

EXPERIMENTAL STUDIES ON IMMUNITY IN DIPHTHERIA

It is now generally believed that the Schick test is a satisfactory method of determining susceptibility to diphtheria, although a negative reaction is no absolute guarantee against contraction of the disease. Top, 1 in a recent survey of the literature, came to the conclusion that there is no reasonable doubt that a person who reacts negatively to the Schick test will resist ordinary risks of infection. Divergencies between the Schick reaction and the content of serum antitoxin have been reported repeatedly. 2 Reports on the occurrence of clinical diphtheria in patients with negative reactions to Schick tests are scarce. A review may be found in an article by Underwood. 3 Recently, Morison and Roberts 4 reported on 146 cases of clinical diphtheria among 18,800 prophylactically treated children. Forty of the children affected had negative Schick reactions after the treatment, while 106 had received three injections of immunizing substance but their