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International Journal of Infectious... Jul 2020To determine the seroprevalence of antibodies against of diphtheria, tetanus, and pertussis among Thai adolescents.
OBJECTIVE
To determine the seroprevalence of antibodies against of diphtheria, tetanus, and pertussis among Thai adolescents.
METHODS
A cross-sectional study was conducted among Thai adolescents aged 11-20 years who had completed five doses of diphtheria, tetanus, and pertussis (DTP)-containing vaccine during childhood, either diphtheria toxoid, tetanus toxoid, whole-cell pertussis (DTwP) or diphtheria toxoid, tetanus toxoid, acellular pertussis (DTaP) vaccine. Protective antibodies against diphtheria, tetanus, and pertussis were defined as anti-diphtheria toxoid IgG ≥0.1 IU/ml, anti-tetanus toxoid IgG ≥0.1 IU/ml, and anti-Bordetella pertussis toxin IgG ≥5 IU/ml, respectively.
RESULTS
Of 220 adolescents (median age 16 years), 45% had received a tetanus toxoid, reduced diphtheria toxoid (Td) booster vaccine during adolescence, and none (0%) had received a tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) booster vaccine. Overall, 50%, 99%, and 57% of adolescents demonstrated protective antibodies against diphtheria, tetanus, and pertussis, respectively. The geometric mean concentrations (GMCs) of antibodies against diphtheria (p = 0.06) and tetanus (p < 0.001) were higher among adolescents who had received Td vaccine. Nevertheless, the antibody levels against both diseases waned over time, regardless of Td booster vaccination. Likewise, pertussis antibody levels gradually declined after the fifth childhood dose of DTwP/DTaP vaccine.
CONCLUSIONS
Approximately half of these healthy Thai adolescents had not maintained protective antibodies against diphtheria and pertussis. A booster vaccination with diphtheria toxoid and/or acellular pertussis-containing vaccines is a crucial strategy to prevent such diseases in this population.
Topics: Adolescent; Adult; Antibodies, Bacterial; Child; Cross-Sectional Studies; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Female; Humans; Immunization, Secondary; Male; Seroepidemiologic Studies; Tetanus; Thailand; Whooping Cough; Young Adult
PubMed: 32387447
DOI: 10.1016/j.ijid.2020.04.088 -
Vaccine Jul 2022The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among...
The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21-1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12-1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94-1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64-0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy.
Topics: Cohort Studies; Corynebacterium; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Infant; Infant, Newborn; Placenta; Pregnancy; Retrospective Studies; Tetanus; Vaccination; Whooping Cough
PubMed: 35717267
DOI: 10.1016/j.vaccine.2022.06.009 -
Scientific Reports Jan 2020Diphtheria is an infectious disease caused by Corynebacterium diphtheriae. The bacterium primarily infects the throat and upper airways and the produced diphtheria toxin...
Diphtheria is an infectious disease caused by Corynebacterium diphtheriae. The bacterium primarily infects the throat and upper airways and the produced diphtheria toxin (DT), which binds to the elongation factor 2 and blocks protein synthesis, can spread through the bloodstream and affect organs, such as the heart and kidneys. For more than 125 years, the therapy against diphtheria has been based on polyclonal horse sera directed against DT (diphtheria antitoxin; DAT). Animal sera have many disadvantages including serum sickness, batch-to-batch variation in quality and the use of animals for production. In this work, 400 human recombinant antibodies were generated against DT from two different phage display panning strategies using a human immune library. A panning in microtiter plates resulted in 22 unique in vitro neutralizing antibodies and a panning in solution combined with a functional neutralization screening resulted in 268 in vitro neutralizing antibodies. 61 unique antibodies were further characterized as scFv-Fc with 35 produced as fully human IgG1. The best in vitro neutralizing antibody showed an estimated relative potency of 454 IU/mg and minimal effective dose 50% (MED50%) of 3.0 pM at a constant amount of DT (4x minimal cytopathic dose) in the IgG format. The targeted domains of the 35 antibodies were analyzed by immunoblot and by epitope mapping using phage display. All three DT domains (enzymatic domain, translocation domain and receptor binding domain) are targets for neutralizing antibodies. When toxin neutralization assays were performed at higher toxin dose levels, the neutralizing capacity of individual antibodies was markedly reduced but this was largely compensated for by using two or more antibodies in combination, resulting in a potency of 79.4 IU/mg in the in vivo intradermal challenge assay. These recombinant antibody combinations are candidates for further clinical and regulatory development to replace equine DAT.
Topics: Animals; Antibodies, Neutralizing; Corynebacterium diphtheriae; Diphtheria Toxin; Epitope Mapping; Guinea Pigs; Humans; Immunoglobulin G; Injections, Intradermal; Models, Molecular; Peptide Elongation Factor 2; Peptide Library; Protein Conformation; Single-Chain Antibodies
PubMed: 31953428
DOI: 10.1038/s41598-019-57103-5 -
Tidsskrift For Den Norske Laegeforening... Mar 2022Persistent itching subcutaneous granulomas related to aluminium-containing vaccines are poorly recognised in health care. They are often associated with aluminium...
BACKGROUND
Persistent itching subcutaneous granulomas related to aluminium-containing vaccines are poorly recognised in health care. They are often associated with aluminium hypersensitivity.
CASE PRESENTATION
An intensely itching subcutaneous nodule appeared on the left thigh of a 17-month-old girl at the injection site for an aluminium adsorbed diphtheria-tetanus-pertussis-polio-HiB vaccine given at 3, 5 and 12 months. Ultrasound suggested a vascular malformation among other differential diagnoses. An MR investigation under general anaesthesia was planned, but the diagnosis was confirmed prior to this by a positive epicutaneous test with aluminium.
INTERPRETATION
Despite a typical history of an itchy vaccination granuloma, the child underwent a thorough hospital workup to rule out malignancy. The diagnosis was delayed for two years. Vaccination granulomas have a good prognosis but can persist for many years. It is important to recognise the condition early in primary health care to avoid unnecessary anxiety and investigations.
Topics: Aluminum; Child; Diphtheria-Tetanus-Pertussis Vaccine; Female; Granuloma; Humans; Infant; Pruritus; Vaccination
PubMed: 35239278
DOI: 10.4045/tidsskr.21.0398 -
Clinical Infectious Diseases : An... Jan 2021The World Health Organization (WHO) does not recommend routine adult booster vaccination for tetanus and diphtheria after completion of the childhood vaccination series.... (Observational Study)
Observational Study
BACKGROUND
The World Health Organization (WHO) does not recommend routine adult booster vaccination for tetanus and diphtheria after completion of the childhood vaccination series. However, many countries continue to implement adult booster vaccinations, leading to the question of whether this is necessary to reduce the incidence of these 2 rare diseases.
METHODS
We conducted an observational cohort study based on WHO case reports from 2001 through 2016. We compared the incidence of tetanus and diphtheria in 31 North American and European countries that either do or do not recommend adult booster vaccination.
RESULTS
Countries that vaccinate adults every 5-20 years (group 1) were compared with countries that do not routinely vaccinate adults for tetanus or diphtheria (group 2). Comparison of group 1 vs group 2 revealed no significant decline in tetanus incidence rates among countries that vaccinate adults (P = .52; risk ratio [RR] = 0.78; 95% confidence interval [CI], .36 to 1.70). The risk of contracting diphtheria was increased among countries that vaccinate adults due to inclusion of Latvia, a country that had poor vaccination coverage (P < .001). However, if Latvia is excluded, there is no difference in diphtheria incidence between countries that do or do not routinely vaccinate adults (P = .26; RR = 2.46; 95% CI, .54 to 11.23).
CONCLUSIONS
Review of >11 billion person-years of incidence data revealed no benefit associated with performing adult booster vaccinations against tetanus or diphtheria. Similar to other vaccines, this analysis supports the WHO position on adult booster vaccination and, if approved by governing health authorities, this may allow more countries to focus healthcare resources on vulnerable and undervaccinated populations.
Topics: Adult; Antibodies, Bacterial; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Europe; Humans; Immunization, Secondary; Incidence; Tetanus; Vaccination; Whooping Cough
PubMed: 32095828
DOI: 10.1093/cid/ciaa017 -
The Lancet. Microbe Aug 2021An outbreak of diphtheria, declared in Yemen in October, 2017, is ongoing. We did a cross-sectional study to investigate the epidemiological, clinical, and...
BACKGROUND
An outbreak of diphtheria, declared in Yemen in October, 2017, is ongoing. We did a cross-sectional study to investigate the epidemiological, clinical, and microbiological features of the outbreak.
METHODS
Probable cases of diphtheria that were defined clinically and recorded through a weekly electronic diseases early warning system (from 2017, week 22, to 2020, week 17) were used to identify trends of the outbreak (we divided the epidemic into three time periods: May 29, 2017, to June 10, 2018; June 11, 2018, to June 3, 2019; and June 4, 2019, to April 26, 2020). We used the line list of diphtheria reports for governorate-level descriptions. Vaccination coverage was estimated using the 2017 and 2018 annual reports by the national Expanded Programme on Immunization. To confirm cases biologically, Corynebacterium diphtheriae was isolated and identified from throat swabs using standard microbiological culture and identification procedures. We assessed differences in the temporal and geographical distributions of cases, including between different age groups. For in-depth microbiological analysis, tox gene and species-specific rpoB real-time PCR, Illumina genomic sequencing, antimicrobial susceptibility analysis (disk diffusion, E-test), and the Elek diphtheria toxin production test were done on confirmed cases. We used genomic data for phylogenetic analyses and to estimate the nucleotide substitution rate.
FINDINGS
The Yemen diphtheria outbreak affected almost all governorates (provinces), with 5701 probable cases and 330 deaths recorded up to April 26, 2020. We collected clinical data for 888 probable cases with throat swab samples referred for biological confirmation, and genomic data for 42 positive cases, corresponding to 43 isolates (two isolates from one culture were included due to distinct colony morphologies). The median age of patients was 12 years (range 0·2-80). The proportion of cases in children aged 0-4 years was reduced during the second time period, after a vaccination campaign, compared with the first period (19% [95% CI 18-21] in the first period vs 14% [12-15] in the second period, p<0·0001). Among 43 tested isolates, 39 (91%) produced the diphtheria toxin and two had low level (0·25 mg/L) antimicrobial resistance to penicillin. We identified six C diphtheriae phylogenetic sublineages, four of which are genetically related to isolates from Saudi Arabia, Eritrea, and Somalia. Inter-sublineage genomic variations in genes associated with antimicrobial resistance, iron acquisition, and adhesion were observed. The predominant sublineage (30 [70%] of 43 isolates) was resistant to trimethoprim and was associated with unique genomic features, more frequent neck swelling (p=0·0029) and a younger age of patients (p=0·060) compared with the other sublineages. Its evolutionary rate was estimated at 1·67 × 10 substitutions per site per year, placing its most recent common ancestor in 2015, and indicating silent circulation of C diphtheriae in Yemen before the outbreak was declared.
INTERPRETATION
In the Yemen outbreak, C diphtheriae shows high phylogenetic, genomic, and phenotypic variation. Laboratory capacity and real-time microbiological monitoring of diphtheria outbreaks need to be scaled up to inform case management and transmission control of diphtheria. Catch-up vaccination might have provided some protection to the targeted population (children aged 0-4 years).
FUNDING
National Centre of the Public Health Laboratories (Yemen), Institut Pasteur, and the French Government Investissement d'Avenir Programme.
TRANSLATION
For the Arabic translation of the abstract see Supplementary Materials section.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Child; Child, Preschool; Corynebacterium; Corynebacterium diphtheriae; Cross-Sectional Studies; Diphtheria; Diphtheria Toxin; Disease Outbreaks; Genomics; Humans; Infant; Middle Aged; Phylogeny; Yemen; Young Adult
PubMed: 35544196
DOI: 10.1016/S2666-5247(21)00094-X -
Genome Medicine Nov 2020Corynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs...
BACKGROUND
Corynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs including first-line penicillin, the genomic determinants and population dynamics of resistance are largely unknown for this neglected human pathogen.
METHODS
Here, we analyzed the associations of antimicrobial susceptibility phenotypes, diphtheria toxin production, and genomic features in C. diphtheriae. We used 247 strains collected over several decades in multiple world regions, including the 163 clinical isolates collected prospectively from 2008 to 2017 in France mainland and overseas territories.
RESULTS
Phylogenetic analysis revealed multiple deep-branching sublineages, grouped into a Mitis lineage strongly associated with diphtheria toxin production and a largely toxin gene-negative Gravis lineage with few toxin-producing isolates including the 1990s ex-Soviet Union outbreak strain. The distribution of susceptibility phenotypes allowed proposing ecological cutoffs for most of the 19 agents tested, thereby defining acquired antimicrobial resistance. Penicillin resistance was found in 17.2% of prospective isolates. Seventeen (10.4%) prospective isolates were multidrug-resistant (≥ 3 antimicrobial categories), including four isolates resistant to penicillin and macrolides. Homologous recombination was frequent (r/m = 5), and horizontal gene transfer contributed to the emergence of antimicrobial resistance in multiple sublineages. Genome-wide association mapping uncovered genetic factors of resistance, including an accessory penicillin-binding protein (PBP2m) located in diverse genomic contexts. Gene pbp2m is widespread in other Corynebacterium species, and its expression in C. glutamicum demonstrated its effect against several beta-lactams. A novel 73-kb C. diphtheriae multiresistance plasmid was discovered.
CONCLUSIONS
This work uncovers the dynamics of antimicrobial resistance in C. diphtheriae in the context of phylogenetic structure, biovar, and diphtheria toxin production and provides a blueprint to analyze re-emerging diphtheria.
Topics: Anti-Bacterial Agents; Corynebacterium diphtheriae; DNA, Bacterial; Diphtheria; Diphtheria Toxin; Drug Resistance, Bacterial; Genes, Bacterial; Genome-Wide Association Study; Genomics; Humans; Macrolides; Metagenomics; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Prospective Studies
PubMed: 33246485
DOI: 10.1186/s13073-020-00805-7 -
BMC Infectious Diseases Jun 2023Diphtheria is a severe respiratory or cutaneous infectious disease, caused by exotoxin producing Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis....
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.
Topics: Animals; Humans; Diphtheria; Netherlands; Travel; Travel-Related Illness; Corynebacterium; Corynebacterium diphtheriae; Exotoxins
PubMed: 37344769
DOI: 10.1186/s12879-023-08388-5 -
Human Vaccines & Immunotherapeutics Jun 2021: Diphtheria-tetanus-pertussis (DTP) vaccine has already been involved in national vaccination program for several decades in China. The immunity against these diseases...
: Diphtheria-tetanus-pertussis (DTP) vaccine has already been involved in national vaccination program for several decades in China. The immunity against these diseases in the people of all ages is not well investigated.: Serum samples were tested for IgG antibodies to diphtheria toxoid (DT), tetanus toxoid (TT) and pertussis toxin (PT) by using commercial ELISA kits.: A total of 666 sera of patients from 1 day to 89 years of age was collected from 2018 to 2019. The protective rates of diphtheria, tetanus and pertussis were 45.5%, 54.4% and 4.7%, respectively. Only 4.7% of the study population had seropositivity against three of the diseases. Young infant (<3 m) and adult (>18y) were generally lack of protective antibody against diphtheria (81.7% and 58.3%) and tetanus (91.5% and 86.2%). An obvious increase in immunity level of diphtheria and tetanus was observed at 3 m-3y, but there was no significant increase of immunity to pertussis at any age group. All age groups showed low immunity to pertussis.: The present results revealed the susceptibility to diphtheria and tetanus in young infants and adults, and the susceptibility to pertussis over the ages, which highlight the need to improve the current vaccination program.
Topics: Adult; Antibodies, Bacterial; China; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Infant; Tetanus; Vaccination; Whooping Cough
PubMed: 33517831
DOI: 10.1080/21645515.2020.1840253 -
American Journal of Preventive Medicine Mar 2022Parental vaccine hesitancy can be a barrier to routine childhood immunization and contribute to greater risk for vaccine-preventable diseases. This study examines the...
Parental Vaccine Hesitancy and Association With Childhood Diphtheria, Tetanus Toxoid, and Acellular Pertussis; Measles, Mumps, and Rubella; Rotavirus; and Combined 7-Series Vaccination.
INTRODUCTION
Parental vaccine hesitancy can be a barrier to routine childhood immunization and contribute to greater risk for vaccine-preventable diseases. This study examines the impact of parental vaccine hesitancy on childhood vaccination rates.
METHODS
This study assessed the association of parental vaccine hesitancy on child vaccination coverage with ≥4 doses of diphtheria, tetanus toxoid, and acellular pertussis vaccine; ≥1 dose of measles, mumps, and rubella vaccine; up-to-date rotavirus vaccine; and combined 7-vaccine series coverage for a sample of children aged 19-35 months using data from the 2018 and 2019 National Immunization Survey-Child (N=7,645). Adjusted differences in multivariable analyses of vaccination coverage were estimated among vaccine hesitant and nonhesitant parents and population attributable risk fraction of hesitancy on undervaccination, defined as not being up to date for each vaccine.
RESULTS
Almost a quarter of parents reported being vaccine hesitant, with the highest proportion of vaccine hesitancy among parents of children who are non-Hispanic Black (37.0%) or Hispanic (30.1%), mothers with a high school education or less (31.9%), and households living below the poverty level (35.6%). Childhood vaccination coverage for all vaccines was lower for children of hesitant than nonhesitant parents, and the population attributable fraction of hesitancy on undervaccination ranged from 15% to 25%, with the highest percentage for ≥1 dose of measles, mumps, and rubella vaccine.
CONCLUSIONS
Parental vaccine hesitancy may contribute up to 25% of undervaccination among children aged 19-35 months. Implementation of strategies to address parental vaccine hesitancy is needed to improve vaccination coverage for children and minimize their risk of vaccine-preventable diseases.
Topics: Child, Preschool; Diphtheria; Humans; Infant; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Mumps; Parents; Pertussis Vaccine; Rotavirus; Rubella; Tetanus Toxoid; Vaccination; Vaccination Hesitancy; Whooping Cough
PubMed: 35190101
DOI: 10.1016/j.amepre.2021.08.015