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International Journal of Molecular... Mar 2022, the etiological agent of diphtheria, is a re-emerging pathogen, responsible for several thousand deaths per year. In addition to diphtheria, systemic infections, often... (Review)
Review
, the etiological agent of diphtheria, is a re-emerging pathogen, responsible for several thousand deaths per year. In addition to diphtheria, systemic infections, often by non-toxigenic strains, are increasingly observed. This indicates that besides the well-studied and highly potent diphtheria toxin, various other virulence factors may influence the progression of the infection. This review focuses on the known components of responsible for adhesion, invasion, inflammation, and cell death, as well as on the cellular signaling pathways activated upon infection.
Topics: Corynebacterium; Corynebacterium diphtheriae; Diphtheria; Diphtheria Toxin; Humans; Virulence Factors
PubMed: 35328715
DOI: 10.3390/ijms23063298 -
Communicable Diseases Intelligence... Jul 2022Diphtheria is rare in Australia, but an increasing number of cases have been notified in recent years. Alongside notifications from 1999 to 2019, we analysed other...
BACKGROUND
Diphtheria is rare in Australia, but an increasing number of cases have been notified in recent years. Alongside notifications from 1999 to 2019, we analysed other relevant national data sources to evaluate trends over the past two decades.
METHODS
Diphtheria notifications (National Notifiable Diseases Surveillance System [NNDSS]), hospitalisations (National Hospital Morbidity Database [NHMD]) and deaths (Australian Bureau of Statistics and the Australian Coordinating Registry) were separately analysed by site of infection, age group, sex, state/territory, Aboriginal and Torres Strait Islander status, and vaccination status.
RESULTS
During the study period, eight (0.002 per 100,000 population per year) cases of respiratory diphtheria and 38 (0.008 per 100,000 population per year) cases of cutaneous diphtheria were recorded in the NNDSS, with 45/46 reported in the nine years since 2011. Corynebacterium diphtheriae accounted for 87% of notified cases, who had a median age of 31.5 years (respiratory diphtheria) and 52.5 years (cutaneous diphtheria); no respiratory diphtheria was notified in those under 15 years of age. A majority of the cutaneous diphtheria cases (27/38; 71%) were acquired overseas, as were 3/8 (38%) of the respiratory diphtheria cases. Rates of both presentation types were higher in Aboriginal and Torres Strait Islander people (respiratory: 0.007 per 100,000 population per year; cutaneous: 0.021 per 100,000 population per year) than were rates in the overall population. Queensland had the highest rate of notified respiratory cases (0.007 per 100,000 population per year), and the Northern Territory the highest rate of cutaneous notifications (0.043 per 100,000 population per year). There were 29 hospitalisations with a principal-diagnosis diphtheria code in the NHMD between 2002 and 2018, of which eight were designated as respiratory (0.002 per 100,000 population per year), eight as cutaneous (0.002 per 100,000 population per year), and 13 with an unknown site of infection. Among notified cases, two deaths were reported in unvaccinated people in Queensland.
CONCLUSIONS
Although diphtheria remains rare in Australia, 45 cases were notified in the years 2011-2019, compared with one case between 1999 and 2010. Robust surveillance remains important to detect all cases. High immunity will need to be maintained across all age groups to prevent outbreaks, and travel and adult booster doses should be encouraged.
Topics: Adult; Disease Outbreaks; Hospitalization; Humans; Northern Territory; Queensland; Vaccine-Preventable Diseases
PubMed: 35860872
DOI: 10.33321/cdi.2022.46.42 -
International Journal of Molecular... Feb 2023In spite of consistent progress at the level of basic research and of clinical treatment, acute myeloid leukemia (AML) still represents an unmet clinical need for adult... (Review)
Review
In spite of consistent progress at the level of basic research and of clinical treatment, acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. To improve the outcomes of these patients, it is necessary to identify new therapeutic targets. IL3RA (CD123, alpha subunit of the interleukin 3 receptor) is a cell membrane protein overexpressed in several hematologic malignancies, including AML blastic plasmocytoid dendritic cell neoplasms (BPDCN). Given the higher expression of CD123 on leukemic cells compared to normal hematopoietic cells and its low/absent expression on normal hematopoietic stem cells, it appears as a suitable and attractive target for therapy. Various drugs targeting CD123 have been developed and evaluated at clinical level: interleukin-3 conjugated with diphtheria toxin; naked neutralizing anti-CD123 antibodies; drug-antibody conjugates; bispecific antibodies targeting both CD123 and CD3; and chimeric antigen receptor (CAR) T cells engineered to target CD123. Some of these agents have shown promising results at the clinical level, including tagraxofusp (CD123 conjugated with diphtheria toxin) for the treatment of BPDCN and IMGN632 (anti-CD123 drug-conjugate), and flotetuzumab (bispecific anti-CD123 and anti-CD3 monoclonal antibody) for the treatment of AML. However, the therapeutic efficacy of CD123-targeting treatments is still unsatisfactory and must be improved through new therapeutic strategies and combined treatments with other antileukemic drugs.
Topics: Adult; Child; Humans; Antineoplastic Agents; Combined Modality Therapy; Dendritic Cells; Diphtheria Toxin; Immunoconjugates; Leukemia, Myeloid, Acute
PubMed: 36769040
DOI: 10.3390/ijms24032718 -
Clinical and Experimental Vaccine... Jan 2022This study aims to compare protection against diphtheria and tetanus conferred on the mother and the neonate before and after maternal vaccination against tetanus,...
PURPOSE
This study aims to compare protection against diphtheria and tetanus conferred on the mother and the neonate before and after maternal vaccination against tetanus, diphtheria, and acellular pertussis (Tdap), transfer of antibodies, and the variables that could impact on the protection.
MATERIALS AND METHODS
The study followed a cohort of 200 pregnant women from a region in Colombia, contacted during prenatal control before vaccination and upon delivery. The work determined immunoglobulin G antibodies against diphtheria and tetanus of pregnant women and umbilical cord. The proportion of protection, the geometric mean of the concentration, and the transfer of maternal antibodies were calculated. The protection profile of the pregnant women was explored by using multiple correspondence analysis.
RESULTS
The concentration of antibodies against diphtheria was significant before and after vaccination of the pregnant women (p=0.000) with proportions of 85.0% and 97.5%, respectively, and of 98.6% in the umbilical cord, with significant antibody correlation (Spearman's coefficient=0.668, p=0.01). Sero-protection against tetanus before vaccination was at 71.0%, after at 92.6%, and in the umbilical cord at 95.9%, with significant antibody concentration before and after vaccination (p=0.000) and antibody correlation (Spearman's coefficient=0.936, p=0.01). Sero-protection was higher when the pregnant women were vaccine 8 to 11 weeks before delivery. Unprotected pregnant women were those not vaccinated during pregnancy.
CONCLUSION
The high proportion of protection against diphtheria and tetanus and the placental transfer support the need to promote maternal immunization with Tdap.
PubMed: 35223667
DOI: 10.7774/cevr.2022.11.1.72 -
Emerging Microbes & Infections Dec 2023Immunization during pregnancy (IP) against pertussis is recommended in many countries to protect infants. Although maternal antibodies can influence the infants'...
Immunization during pregnancy (IP) against pertussis is recommended in many countries to protect infants. Although maternal antibodies can influence the infants' antibody responses to primary vaccinations, their effect on the development of functional antibodies and B cells remain poorly studied. We investigated the maternal immune response to IP and the effect of IP and pre-existing antibodies on infants' primary vaccine responses in an open-label, non-randomized trial. Forty-seven mothers received tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy, and 22 mothers were included as controls. Sixty-nine infants received primary doses of DTaP at three and five months of age. Geometric mean concentrations of antibodies to pertussis toxin, filamentous haemagglutinin, pertactin, diphtheria, and tetanus toxins, pertussis toxin neutralizing antibodies (PTNAs), and plasma and memory B-cell frequencies were studied at delivery, and at three, five and six months. Levels of antibodies, PTNAs, and frequencies of memory B-cells were significantly increased at delivery and up to six months after in mothers with IP compared to those without IP (all < 0.05, except for PT-specific memory B-cells). In vaccinated pregnant women, high pre-existing antibody levels were positively correlated with higher antibody responses after IP. IP blunted the infants' antibody and plasma B-cell responses to all vaccine antigens, except for tetanus toxin. This blunting effect was the strongest in infants with high concentrations of maternal antibodies. In conclusion, IP resulted in significantly higher concentrations of antibodies in infants up to three months of age (all < 0.05); but was associated with blunting of various infants' vaccine responses.
Topics: Humans; Infant; Female; Pregnancy; Diphtheria-Tetanus-acellular Pertussis Vaccines; Whooping Cough; Pertussis Toxin; Diphtheria; Antibodies, Bacterial; Vaccination; Immunization
PubMed: 37060181
DOI: 10.1080/22221751.2023.2204146 -
Journal of Pharmaceutical Sciences Jan 2020Diphtheria toxoid is produced by detoxification of diphtheria toxin with formaldehyde. This study was performed to elucidate the chemical nature and location of...
Diphtheria toxoid is produced by detoxification of diphtheria toxin with formaldehyde. This study was performed to elucidate the chemical nature and location of formaldehyde-induced modifications in diphtheria toxoid. Diphtheria toxin was chemically modified using 4 different reactions with the following reagents: (1) formaldehyde and NaCNBH, (2) formaldehyde, (3) formaldehyde and NaCNBH followed by formaldehyde and glycine, and (4) formaldehyde and glycine. The modifications were studied by SDS-PAGE, primary amino group determination, and liquid chromatography-electrospray mass spectrometry of chymotryptic digests. Reaction 1 resulted in quantitative dimethylation of all lysine residues. Reaction 2 caused intramolecular cross-links, including the NAD-binding cavity and the receptor-binding site. Moreover, A fragments and B fragments were cross-linked by formaldehyde on part of the diphtheria toxoid molecules. Reaction 3 resulted in formaldehyde-glycine attachments, including in shielded areas of the protein. The detoxification reaction typically used for vaccine preparation (reaction 4) resulted in a combination of intramolecular cross-links and formaldehyde-glycine attachments. Both the NAD-binding cavity and the receptor-binding site of diphtheria toxin were chemically modified. Although CD4 T-cell epitopes were affected to some extent, one universal CD4 T-cell epitope remained almost completely unaltered by the treatment with formaldehyde and glycine.
Topics: Borohydrides; Chromatography, Reverse-Phase; Diphtheria Toxin; Diphtheria Toxoid; Drug Compounding; Electrophoresis, Polyacrylamide Gel; Epitopes, T-Lymphocyte; Formaldehyde; Glycine; Models, Molecular; Protein Conformation; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship
PubMed: 31678246
DOI: 10.1016/j.xphs.2019.10.047 -
Epidemiology and Infection Aug 2023National vaccination programmes recommend the influenza vaccine for older adults, but this population group has the greatest morbidity and mortality from other...
National vaccination programmes recommend the influenza vaccine for older adults, but this population group has the greatest morbidity and mortality from other preventable vaccine diseases. The aim of this article is to estimate the vaccine coverage in adults aged 65 years and older and to analyse the factors that could increase or decrease vaccination uptake probability for the three listed vaccines in the national vaccination programme (influenza, tetanus and diphtheria, and pneumococcus) and the full scheme in Mexico. We conducted an analytical cross-sectional study with 2012, 2018, and 2021 rounds from the National Health and Nutrition Survey, in which we calculated the vaccine coverage estimations and performed multivariable logistic regression models to analyse the factors related to vaccine uptake. Tetanus and diphtheria vaccines had the greatest coverage estimation in all years (59-71%), whereas the pneumococcus vaccine had the lowest (32-53%). Full scheme vaccine coverage decreased from 37.80% to 24.77% in 2012 and 2021, respectively. The National Health Card property, morbidity, being a beneficiary of any health system institution, and use of preventive services increased the probability of vaccine uptake. In conclusion, vaccine coverage in older Mexican adults decreased over time, and the Mexican health system plays a strategic role in immunisation.
Topics: Aged; Humans; Cross-Sectional Studies; Diphtheria; Influenza Vaccines; Mexico; Tetanus; Tetanus Toxoid; Vaccination; Vaccination Coverage
PubMed: 37577972
DOI: 10.1017/S0950268823001218 -
Transplantation and Cellular Therapy Apr 2023Revaccination against tetanus and diphtheria after allogeneic hematopoietic stem cell transplantation (HCT) is usually effective, but the duration of the immunity is...
Revaccination against tetanus and diphtheria after allogeneic hematopoietic stem cell transplantation (HCT) is usually effective, but the duration of the immunity is unknown. We conducted this study to evaluate humoral immunity to tetanus and diphtheria in long-term survivors and to provide knowledge regarding the need for boosters. The median time from HCT to blood sampling was 14 years (range, 8 to 40 years). All patients had received at least 3 doses of vaccines against both tetanus and diphtheria, either monovalent or combination vaccines containing a full dose of the diphtheria toxoid component. In addition, 1 or more booster doses were administered to 21 of the 146 patients (14%). On enzyme-linked immunosorbent assay, levels <.1 IU/mL for diphtheria and <.01 IU/mL for tetanus were considered low or seronegative. Values between .01 and .5 IU/mL for tetanus and between .1 and 1.0 IU/mL for diphtheria were considered to represent partial protection, and levels >.5 and >1.0 IU/mL were considered high and protective, respectively. In all, 39% of patients were seronegative against diphtheria, 52% had some protection, and 9% had a high titer. In contrast, no patient had become seronegative to tetanus, 32% had "partial protection" against tetanus and 68% had a high titer. In multivariate analysis, active graft-versus-host-disease, sex, or time from sampling did not affect the probability of becoming seronegative or seropositive. Younger age was associated with lower antibody levels to tetanus toxoid, but age was not correlated with antibody levels against diphtheria toxoid. Tetanus immunity was maintained after vaccination in most long-term survivors, but immunity against diphtheria was poor, and boosters should be considered.
Topics: Humans; Diphtheria; Tetanus; Antibodies, Bacterial; Tetanus Toxoid; Vaccination; Diphtheria Toxoid; Corynebacterium; Hematopoietic Stem Cell Transplantation
PubMed: 36720458
DOI: 10.1016/j.jtct.2023.01.023 -
MMWR. Morbidity and Mortality Weekly... Oct 2023In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), the 2021-2030 global strategy that envisions a world where everyone, everywhere, at...
In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), the 2021-2030 global strategy that envisions a world where everyone, everywhere, at every age, fully benefits from vaccines. This report reviews trends in World Health Organization and UNICEF immunization coverage estimates at global, regional, and national levels through 2022 and documents progress toward improving coverage with respect to the IA2030 strategy, which aims to reduce the number of children who have not received the first dose of a diphtheria-tetanus-pertussis-containing vaccine (DTPcv1) worldwide by 50% and to increase coverage with 3 diphtheria-tetanus-pertussis-containing vaccine doses (DTPcv3) to 90%. Worldwide, coverage ≥1 dose of DTPcv1 increased from 86% in 2021 to 89% in 2022 but remained below the 90% coverage achieved in 2019. Estimated DTPcv3 coverage increased from 81% in 2021 to 84% in 2022 but also remained below the 2019 coverage of 86%. Worldwide in 2022, 14.3 million children were not vaccinated with DTPcv1, a 21% decrease from 18.1 million in 2021, but an 11% increase from 12.9 million in 2019. Most children (84%) who did not receive DTPcv1 in 2022 lived in low- and lower-middle-income countries. COVID-19 pandemic-associated immunization recovery occurred in 2022 at the global level, but progress was unevenly distributed, especially among low-income countries. Urgent action is needed to provide incompletely vaccinated children with catch-up vaccinations that were missed during the pandemic, restore national vaccination coverage to prepandemic levels, strengthen immunization programs to build resiliency to withstand future unforeseen public health events, and further improve coverage to protect children from vaccine-preventable diseases.
Topics: Child; Humans; Infant; Vaccination Coverage; Diphtheria; Pandemics; Tetanus; Whooping Cough; Immunization Programs; Vaccination; Diphtheria-Tetanus-Pertussis Vaccine; Immunization Schedule
PubMed: 37883326
DOI: 10.15585/mmwr.mm7243a1 -
Indian Pediatrics Mar 2021To determine seroprotective titres for diphtheria, pertussis, tetanus and measles in children with nephrotic syndrome who had received essential immunization.
OBJECTIVE
To determine seroprotective titres for diphtheria, pertussis, tetanus and measles in children with nephrotic syndrome who had received essential immunization.
METHODS
Children (2-18 years) with steroid sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome (SRNS) who were in disease remission and had received essential childhood immunization were included. Anti-diphtheria, anti-pertussis, anti-tetanus and anti-measles antibody titres were measured.
RESULTS
Seventy-six (40 with SSNS; 36 with SRNS) children with mean (SD) age 7.54 (3.96) years were enrolled. The time elapsed since last vaccination was >5 years in 68.4% patients. The seroprotection rates for diphtheria, tetanus, pertussis, and measles were 86.8%, 93.4%, 31.6% and 77.6% respectively; lower in SRNS subjects compared to SSNS. Robust seroprotection titers (1.0 IU/mL) for diphtheria were seen in 23.8% SSNS and 17.9% SRNS; P=0.04, and for tetanus in 69.3% SSNS and 43.8% of SRNS subjects; P=0.03, respectively.
CONCLUSIONS
Children with nephrotic syndrome especially those with SRNS have lower seroprotective titers for diphtheria, tetanus, pertussis and measles, necessitating a booster dose of DPT/DT/Td and MR/MMR.
Topics: Antibodies, Bacterial; Child; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Immunization, Secondary; Measles; Nephrotic Syndrome; Tetanus; Whooping Cough
PubMed: 33713058
DOI: No ID Found