-
Microbiology Spectrum Aug 2022Diphtheria is rare in the United States. and many industrialized nations due to development of an effective vaccine, coupled with high vaccination coverage. Although...
Diphtheria is rare in the United States. and many industrialized nations due to development of an effective vaccine, coupled with high vaccination coverage. Although there is continued risk of importation and transmission of Corynebacterium diphtheriae, C. ulcerans has now become the dominant source of diphtheria cases among several European countries. Bearing this in mind, a better understanding of C. ulcerans biology is clearly needed. Here, we identified active transmission of toxigenic C. ulcerans among indoor- and outdoor-housed rhesus macaques based on diphtheria toxin-specific serology assays as well as direct isolation of C. ulcerans from a recently infected animal. In addition to animal-to-animal transmission, we found serological evidence indicative of potential human transmission. Together, these results provide new details on natural Corynebacterium transmission among nonhuman primates and emphasizes the importance of maintaining high vaccination coverage to reduce the risk of potential zoonotic infection. C. ulcerans represents an emerging zoonotic agent of diphtheria, but little is known about its transmission or maintenance among animal reservoirs. In these studies, we identified diphtheria outbreaks among both outdoor- and indoor-housed rhesus macaques and isolated a toxigenic strain of C. ulcerans from a recently infected animal. Retrospective analysis indicated that toxigenic have been circulating among these primates for decades with the potential for rare zoonotic transmission to humans.
Topics: Animals; Corynebacterium; Diphtheria; Humans; Macaca mulatta; Retrospective Studies
PubMed: 35863003
DOI: 10.1128/spectrum.00894-22 -
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 -
The Journal of Infectious Diseases Feb 2022Pertussis, diphtheria, and tetanus (DTP)-containing vaccines combined with polio vaccines are recommended by the World Health Organization as part of routine... (Meta-Analysis)
Meta-Analysis
Pertussis, diphtheria, and tetanus (DTP)-containing vaccines combined with polio vaccines are recommended by the World Health Organization as part of routine immunization programs. The decline of immunity after vaccination has been considered as a possible reason for the reemergence of vaccine-preventable diseases worldwide. In this study, we evaluated the potential duration of protective immunity of pertussis, diphtheria, tetanus, and polio through a systematic review and meta-analysis. We examined data on immunological and clinical outcomes. We observed evidence of waning postvaccination immunity for pertussis and diphtheria, whereas tetanus and polio vaccines provided sustained protection. Further research on the risk factors of waning immunity after vaccination and the optimal timing of booster doses for pertussis and diphtheria is needed.
Topics: Antibodies, Bacterial; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines; Humans; Immunization, Secondary; Poliomyelitis; Tetanus; Vaccination; Vaccines, Combined; Whooping Cough
PubMed: 34543411
DOI: 10.1093/infdis/jiab480 -
The National Medical Journal of India 2017
Topics: Diphtheria; Emergency Service, Hospital; Foot Ulcer; Hospitals, Rural; Humans; Hydronephrosis; India; Poverty Areas; Rural Population; Vulnerable Populations
PubMed: 29916437
DOI: 10.4103/0970-258X.234403 -
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 -
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 -
International Journal of Pediatric... Jan 2018To study the cardiac complications in diphtheria patients and to study the predictors of outcomes.
OBJECTIVE
To study the cardiac complications in diphtheria patients and to study the predictors of outcomes.
STUDY DESIGN
Single centre prospective analysis of cardiac complications in diphtheria patients.
RESULTS
In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%).
CONCLUSION
Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Creatine Kinase; Diphtheria; Electrocardiography; Female; Heart Diseases; Humans; Infant; Male; Prospective Studies; Sensitivity and Specificity; Troponin T
PubMed: 29287886
DOI: 10.1016/j.ijporl.2017.10.032 -
Vaccine Nov 2018The Advisory Committee for Immunization Practices recommends that all pregnant women receive the seasonal influenza vaccine and the tetanus toxoid, diphtheria toxoid,... (Review)
Review
BACKGROUND
The Advisory Committee for Immunization Practices recommends that all pregnant women receive the seasonal influenza vaccine and the tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine during every pregnancy. However, vaccination coverage rates are suboptimal among pregnant women in the United States, leaving these women and their unborn children at risk of vaccine-preventable diseases and their complications.
OBJECTIVES
We sought to understand the current landscape of published literature regarding maternal immunization, including barriers to and predictors of vaccine acceptance, and identify gaps in the research in order to inform strategies for future programmatic improvement.
METHODS
We conducted a literature search using MEDLINE (OVID), PsychINFO, and CINAHL (Ebsco) databases. The search included published, English-language manuscripts that identified patient, provider, or system-level barriers to, predictors of, or interventions that improved uptake of maternal vaccines among pregnant women in the US. Studies were reviewed using an inductive thematic analysis approach.
RESULTS
We included 75 studies in our review. Pregnant women identified 25 different barriers to accepting recommended maternal immunizations; barriers related to vaccine safety perceptions were the most common. Healthcare providers identified 24 different barriers to vaccinating their pregnant patients. The most commonly cited barriers among healthcare providers were financial concerns. Eighteen different predictors of vaccine acceptance were identified. Receipt of a healthcare provider's recommendation was the factor most frequently reported as a reason for vaccination among pregnant women.
CONCLUSIONS
We were able to identify gaps in the literature regarding maternal immunization and make recommendations for future research. Efforts to address the challenges of maternal immunization in the United States should include increasing the focus on Tdap, implementing more high-level assessments of safety perceptions and associated concerns, and determining most effective interventions.
Topics: Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Influenza Vaccines; Pregnancy; Pregnant Women; Tetanus; United States; Vaccination Coverage; Whooping Cough
PubMed: 30377064
DOI: 10.1016/j.vaccine.2018.10.046 -
Expert Review of Vaccines 2023This study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)'s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of an indigenously developed tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine (Tdap) in adults, adolescents, and children in India.
BACKGROUND
This study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)'s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster vaccine (Tdap).
RESEARCH DESIGN AND METHODS
In this Phase II/III, multicenter, randomized, active-controlled, open-label study, 1500 healthy individuals, aged 4-65 years, were randomized to receive a single dose of SIIPL Tdap or comparator Tdap vaccine (Boostrix®; GlaxoSmithKlines, India). Adverse events (AEs) during initial 30 minutes, 7-day, 30-day post-vaccination were assessed. Blood samples were taken before and 30 days post-vaccination for immunogenicity assessment.
RESULTS
No significant differences in incidence of local and systemic solicited AEs were observed between the two groups; no vaccine-related serious AEs were reported. SIIPL Tdap was non-inferior to comparator Tdap in achieving booster responses to TT and DT in 75.2% and 70.8% of the participants, respectively, and to pertussis toxoid (PT), pertactin (PRN), and filamentous hemagglutinin (FHA) in 94.3%, 92.6%, and 95.0% of the participants, respectively. Anti-PT, anti-PRN, and anti-FHA antibody geometric mean titers in both the groups, were significantly higher post-vaccination compared to pre-vaccination.
CONCLUSIONS
Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to immunogenicity against tetanus, diphtheria, and pertussis and was well tolerated.
Topics: Adult; Humans; Adolescent; Child; Tetanus Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines; Whooping Cough; Tetanus; Diphtheria Toxoid; Pertussis Vaccine; Toxoids; Immunization, Secondary; Diphtheria; Antibodies, Bacterial
PubMed: 36883291
DOI: 10.1080/14760584.2023.2188942