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Frontiers in Public Health 2019() is a relatively rare pathogen in most Western countries. While toxin producing strains can cause pharyngeal diphtheria with potentially fatal outcomes, the more... (Review)
Review
() is a relatively rare pathogen in most Western countries. While toxin producing strains can cause pharyngeal diphtheria with potentially fatal outcomes, the more common presentation is wound infections. The diphtheria toxin is encoded on a prophage and can also be carried by and . Currently, across Europe, infections are mainly diagnosed in travelers and refugees from regions where diphtheria is more endemic, patients from urban areas with poor hygiene, and intravenous drug users. About half of the cases are non-toxin producing isolates. Rapid identification of the bacterial pathogen and toxin production is a critical element of patient and outbreak management. Beside the immediate clinical management of the patient, public health agencies should be informed of toxigenic diagnoses as soon as possible. The collection of case-related epidemiological data from the patient is often challenging due to language barriers and social circumstances. However, information on patient contacts, vaccine status and travel/refugee route, where appropriate, is critical, and should be documented. In addition, isolates should be characterized using high resolution typing, in order to identify transmissions and outbreaks. In recent years, whole genome sequencing (WGS) has become the gold standard of high-resolution typing methods, allowing detailed investigations of pathogen transmissions. De-centralized sequencing strategies with redundancy in sequencing capacities, followed by data exchange may be a valuable future option, especially since WGS becomes more available and portable. In this context, the sharing of sequence data, using public available platforms, is essential. A close interaction between microbiology laboratories, treating physicians, refugee centers, social workers, and public health officials is a key element in successful management of suspected outbreaks. Analyzing bacterial isolates at reference centers may further help to provide more specialized microbiological techniques and to standardize information, but this is also more time consuming during an outbreak. Centralized communication strategies between public health agencies and laboratories helps considerably in establishing and coordinating effective surveillance and infection control. We review the current literature on high-resolution typing of and share our own experience with the coordination of a Swiss-German outbreak.
PubMed: 31497588
DOI: 10.3389/fpubh.2019.00235 -
International Journal of Infectious... Dec 2023During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China.
OBJECTIVES
During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage.
METHODS
This study was a follow-up trial of the "Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial." Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines.
RESULTS
The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period.
CONCLUSION
Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.
Topics: Child; Humans; Infant; Diphtheria-Tetanus-acellular Pertussis Vaccines; Measles-Mumps-Rubella Vaccine; Poliovirus Vaccine, Inactivated; Pandemics; Vaccines, Combined; Poliovirus; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Antibodies, Bacterial; Immunization Schedule
PubMed: 37832931
DOI: 10.1016/j.ijid.2023.10.006 -
Epidemiology and Infection Jan 2022Diphtheria is a potentially devastating disease whose epidemiology remains poorly described in many settings, including Madagascar. Diphtheria vaccination is delivered...
Diphtheria is a potentially devastating disease whose epidemiology remains poorly described in many settings, including Madagascar. Diphtheria vaccination is delivered in combination with pertussis and tetanus antigens and coverage of this vaccine is often used as a core measure of health system functioning. However, coverage is challenging to estimate due to the difficulty in translating numbers of doses delivered into numbers of children effectively immunised. Serology provides an alternative lens onto immunisation, but is complicated by challenges in discriminating between natural and vaccine-derived seropositivity. Here, we leverage known features of the serological profile of diphtheria to bound expectations for vaccine coverage for diphtheria, and further refine these using serology for pertussis. We measured diphtheria antibody titres in 185 children aged 6-11 months and 362 children aged 8-15 years and analysed them with pertussis antibody titres previously measured for each individual. Levels of diphtheria seronegativity varied among age groups (18.9% of children aged 6-11 months old and 11.3% of children aged 8-15 years old were seronegative) and also among the districts. We also find surprisingly elevated levels of individuals seropositive to diphtheria but not pertussis in the 6-11 month old age group suggesting that vaccination coverage or efficacy of the pertussis component of the DTP vaccine remains low or that natural infection of diphtheria may be playing a significant role in seropositivity in Madagascar.
Topics: Adolescent; Antibodies, Bacterial; Bordetella pertussis; Child; Corynebacterium diphtheriae; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Female; Humans; Immunization Programs; Immunoglobulin G; Infant; Madagascar; Male; Seroepidemiologic Studies; Vaccination Coverage; Whooping Cough
PubMed: 35229710
DOI: 10.1017/S0950268822000097 -
Journal of Family Medicine and Primary... Oct 2019Outbreaks of diphtheria continue to occur in Kerala with an age shift to older population. Antibody seroprevalence studies are essential to understand the immune status...
UNLABELLED
Outbreaks of diphtheria continue to occur in Kerala with an age shift to older population. Antibody seroprevalence studies are essential to understand the immune status of the community and to develop an effective immunization strategy.
AIM
To assess the necessity of diphtheria vaccination among adults.
SETTINGS AND DESIGN
Cross-sectional study, among 152 healthy adults (>18 years).
METHODS AND MATERIALS
Diphtheria IgG antibody detection was performed by using ELISA technique.
RESULTS
Out of 152 study population, 14 (9.2%) individuals had very low antibody levels, requiring basic immunization, 123 (80.9%) needed booster vaccination, 12 (7.9%) would need a booster dose in 5 years and 3 (2%) would need a booster dose in 7 years to maintain adequate antibody levels. Out of the total, 131 (86.2%) individuals had completed childhood immunization and 21 (13.8%) had incomplete or no immunization during childhood. In the population who had completed childhood immunization, 4 (3%) had very low antibody levels requiring basic immunization and 113 (86%) had antibody levels needing booster vaccine soon, with the remaining 14 (10.6%) individuals requiring a booster vaccine after 5 years and 7 years. In the partially immunized/unimmunized population, 10 (47.6%) had antibody levels requiring basic immunization and another 10 (47.6%) had antibody levels low enough to warrant a booster vaccine.
CONCLUSIONS
Majority of the subjects who had completed childhood immunization showed an inadequate immunity against diphtheria during adulthood. This indicates waning immunity against diphtheria. Hence, modifying the present diphtheria vaccination strategy to include booster doses during adulthood is essential.
CONTEXT
Even in developed countries where nearly 100% universal immunization is achieved, diphtheria outbreaks are known to occur. Several seroprevalence studies have been conducted in those regions to determine whether those populations have adequate levels of antibodies against diphtheria. In India, sporadic outbreaks occur, and an increasing number of diphtheria cases are being reported over the last few years. Large outbreaks in Kerala 2016 were about 533 cases. Recent outbreaks in 2019, in Trivandrum, about 175 cases were suspected and 19 cases were confirmed in laboratory. However, Indian studies to determine whether the adult population has adequate protective antibody levels are lacking. Knowing the immune status of the population and devising an appropriate strategies to prevent outbreaks of diphtheria are the integral parts of primary care. These concerns are the basis and evaluation of the seroprevalence of IgG antibody levels against diphtheria antitoxin among healthy adults in our region in this study.
PubMed: 31742151
DOI: 10.4103/jfmpc.jfmpc_589_19 -
Public Health in Practice (Oxford,... Jun 2023The objective of this short communication is to summarize the current situation in Pakistan regarding the rising cases of diphtheria and to emphasize the need for public...
BACKGROUND
The objective of this short communication is to summarize the current situation in Pakistan regarding the rising cases of diphtheria and to emphasize the need for public health interventions to control the spread of the disease.
STUDY DESIGN
This study is a short communication.
METHODS
Data on diphtheria cases were collected from various sources including the Pakistan Ministry of Health, the World Health Organization (WHO), and media reports. Descriptive statistics were used to summarize the data on the number of cases and trends over time.
RESULTS
As of 2023, the number of reported diphtheria cases in Pakistan has increased by 50% compared to the previous year. The majority of cases are being reported from the Sindh and Punjab provinces. The incidence of diphtheria is highest among children under the age of 10.
CONCLUSIONS
The rising cases of diphtheria in Pakistan are a cause for concern and indicate the need for effective public health interventions to control the spread of the disease. This includes increasing vaccine coverage, improving hygiene practices, and enhancing surveillance and reporting systems. The public health community should also work towards educating communities on the importance of vaccination and preventative measures to reduce the burden of diphtheria in Pakistan.
PubMed: 37293529
DOI: 10.1016/j.puhip.2023.100395 -
Vaccine Nov 2023Diphtheria is rare in England because of an effective national immunisation schedule that includes 5 doses of a diphtheria-containing vaccine at 2, 3, 4 months,...
BACKGROUND
Diphtheria is rare in England because of an effective national immunisation schedule that includes 5 doses of a diphtheria-containing vaccine at 2, 3, 4 months, preschool and adolescent boosters. However, in recent years there has been a notable increase in cases due to Corynebacterium ulcerans among older adults and evidence of endemic transmission of C. diphtheriae (normally associated with travel to endemic countries). We aimed to update 2009 estimates of diphtheria immunity considering the evolving epidemiology.
METHODS
Residual sera collected from diagnostic laboratories and general practitioners in England in 2021 were randomly selected and tested for diphtheria antibody, to estimate proportions protected per age group. Diphtheria antibody levels were defined as susceptible (<0.01 IU/mL), basic protection (0.01-0.099 IU/mL) and full protection (≥0.1 IU/mL). Immunity estimates were standardised to the England population and compared to 2009.
RESULTS
Based on 3,745 residual sera tested, 89% (95%CI: 87%-90%) of the 2021 England population had at least basic diphtheria protection (vs. 90% [88%-92%] in 2009) and 50% (48%-52%) full protection (vs. 41% [38%-44%]). Higher antibody levels were observed in those aged 1 and under, 10-11, 12-15, 25-34 and 35-44 years compared to 2009. The largest proportion susceptible were observed in those aged 70+, 26% (21%-31%) vs 12% (7%-18%) in 2009.
CONCLUSIONS
Basic diphtheria protection is comparable between 2021 and 2009. The increase in immunity in working age adults is likely due to the school leaver booster introduced in 1994. The current vaccination schedule is maintaining sufficient population immunity. However, we recommend clinicians remain vigilant to severe diphtheria outcomes in older adults, because of their observed susceptibility.
Topics: Humans; Diphtheria; England; Adolescent; Adult; Young Adult; Child; Child, Preschool; Aged; Middle Aged; Antibodies, Bacterial; Male; Female; Infant; Seroepidemiologic Studies; Aged, 80 and over; Diphtheria Toxoid
PubMed: 37821313
DOI: 10.1016/j.vaccine.2023.10.003 -
Evolution, Medicine, and Public Health 2022Some vaccines, such as diphtheria toxoid and acellular pertussis vaccines (aPVs), may favor the emergence of less pathogenic strains of the respective bacteria they... (Review)
Review
Some vaccines, such as diphtheria toxoid and acellular pertussis vaccines (aPVs), may favor the emergence of less pathogenic strains of the respective bacteria they target. This review discusses the impact of the wide use of aPV on phenotype evolutions and their beneficial consequences in the light of the diphtheria toxoid immunization program experience and structuring evidence review in a causal analysis following Bradford Hill's causality criteria. All aPVs contain the pertussis toxin (PT), the main virulence factor of , alone or with one adhesin (filamentous hemagglutinin (FHA)), two adhesins (FHA and pertactin (PRN)) or four adhesins (FHA, PRN and two fimbriae (Fim 2/3)). In countries where the coverage of aPVs containing PRN is high, PRN negative isolates are increasing in prevalence, but isolates nonproducing the other antigens are rarely reported. We hypothesize that the selective pressure at play with PRN should exist against all aVP antigens, although detection biases may hinder its detection for other antigens, especially PT. PT being responsible for clinically frank cases of the disease, the opportunity to collect PT negative isolates is far lower than to collect PRN negative isolates which have a limited clinical impact. The replacement of the current by far less pathogenic isolates no longer producing the factors contained in aPVs should be expected as a consequence of the wide aPV use.
PubMed: 36032328
DOI: 10.1093/emph/eoac028 -
Vaccines Mar 2021The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon...
The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. One-hundred and twelve 15 mer peptides covering the entire sequence of diphtheria toxin (DTx) protein were prepared by SPOT synthesis. The immunoreactivity of membrane-bound peptides with sera from mice immunized with a triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, multiantigen peptide (MAP) synthesis, and Enzyme-Linked Immunosorbent Assay (ELISA) development. Twenty epitopes were identified, with two being in the signal peptide, five in the catalytic domain (CD), seven in the HBFT domain, and five in the receptor-binding domain (RBD). Two 17 mer (CB/Tx-2/12 and CB/DTx-4-13) derived biepitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccinated sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) for huVS and miVS and, when compared with a commercial ELISA test, demonstrated a high performance. Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated sufficient specificity and eligibility for phase IIB studies of some epitopes to develop new and fast diagnostic assays.
PubMed: 33810325
DOI: 10.3390/vaccines9040313 -
Annals of Allergy, Asthma & Immunology... Sep 2023Pertussis is a highly contagious respiratory disease, and those with chronic respiratory illnesses may be at higher risk of infection and severe pertussis. Acellular... (Observational Study)
Observational Study
BACKGROUND
Pertussis is a highly contagious respiratory disease, and those with chronic respiratory illnesses may be at higher risk of infection and severe pertussis. Acellular pertussis-containing vaccines (Tdap) are recommended in the United States for those with risk factors, such as asthma and chronic obstructive pulmonary disease (COPD).
OBJECTIVE
To determine Tdap vaccination rates among people with asthma or COPD compared with matched controls with type 2 diabetes and the general population.
METHODS
This observational database study identified adults with asthma or COPD, and their matched controls, from a large US administrative health claims system between January 2008 and December 2014. Vaccination with Tdap was identified using current procedural terminology and national drug codes, and vaccination rates per 1000 patient-years and adjusted rate ratios (RR) were calculated using a generalized linear model with a Poisson distribution and 95% confidence intervals (CI).
RESULTS
Vaccination rates were low overall; however, they were slightly higher in asthma than the general population cohort, with vaccination incidence RRs of 1.12 (95% CI, 1.08-1.17), 1.09 (95% CI, 1.06-1.11), and 1.11 (95% CI, 1.07-1.16) in those aged 18 to 44, 45 to 64, and 65 years and older, respectively. However, Tdap vaccination rates were lower in the COPD than in the general population cohort, with vaccination incidence RRs of 0.72 (95% CI, 0.60-0.86), 0.87 (95% CI, 0.83-0.91), and 0.94 (95% CI, 0.92-0.96), respectively.
CONCLUSION
Pertussis vaccination rates were suboptimal among adults in general and adults with asthma or COPD. Work is needed to boost Tdap vaccination uptake among people with chronic respiratory conditions.
Topics: Humans; Adult; United States; Tetanus; Diphtheria-Tetanus-acellular Pertussis Vaccines; Diphtheria; Whooping Cough; Diabetes Mellitus, Type 2; Pulmonary Disease, Chronic Obstructive; Asthma
PubMed: 37080456
DOI: 10.1016/j.anai.2023.04.008 -
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