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Immunity, Inflammation and Disease Nov 2023The introduction of the diphtheria-tetanus-pertussis (DTP) vaccine into childhood immunization programs resulted in its widespread elimination in high-income countries.... (Review)
Review
INTRODUCTION
The introduction of the diphtheria-tetanus-pertussis (DTP) vaccine into childhood immunization programs resulted in its widespread elimination in high-income countries. However, Nigeria is currently experiencing an outbreak. The primary cause of diphtheria outbreaks and its high mortality rates in Nigeria was waning herd immunity due to low DTP coverage and a lack of diphtheria antitoxin (DAT), respectively. However, the underlying causes of Nigeria's low DTP coverage and DAT supply remain unknown.
METHOD
Relevant studies and reports included in our review were obtained by a search through Google Scholar, PubMed, and organization websites using the terms "Diphtheria-Pertussis-Tetanus vaccine OR Diphtheria antitoxin and Nigeria OR Diphtheria Outbreak." All articles considering diphtheria outbreaks, DTP vaccine, and DAT supply in Nigeria were considered without time restriction due to the paucity of data. We used the narrative synthesis approach to critically appraise, analyze, and draw inferences from the selected articles.
RESULTS
The main causes of low DTP coverage are insufficient supply, an inefficient cold chain system, and low uptake due to poor health literacy and negative sociocultural and religious beliefs, whereas the key barriers to DAT availability are insufficient production by pharmaceutical industries because of low demand and priority.
CONCLUSION
The underlying causes of Nigeria's low DTP coverage and DAT supply are multifactorial. Both short-term and long-term measures are needed to control this outbreak and prevent future occurrences.
Topics: Humans; Child; Diphtheria; Diphtheria Antitoxin; Nigeria; Diphtheria-Tetanus-Pertussis Vaccine; Corynebacterium; Disease Outbreaks
PubMed: 38018582
DOI: 10.1002/iid3.1096 -
Euro Surveillance : Bulletin Europeen... Feb 2022BackgroundDiphtheria is uncommon in the World Health Organization (WHO) European Region. Nevertheless, sporadic cases, sometimes fatal, continue to be reported.AimTo...
BackgroundDiphtheria is uncommon in the World Health Organization (WHO) European Region. Nevertheless, sporadic cases, sometimes fatal, continue to be reported.AimTo report on diphtheria cases and coverage with first and third doses of diphtheria, tetanus and pertussis vaccines (DTP1 and DTP3, respectively) for 2010-19 in the Region with a focus on 2019.MethodsData on diphtheria cases were obtained from WHO/United Nations International Children's Emergency Fund (UNICEF) Joint Reporting Forms submitted annually by the Region's Member States. WHO/UNICEF Estimates of National Immunization Coverage for DTP1 and DTP3 were summarised for 2010-19. For 2019, we analysed data on age, and vaccination status and present data by country on DTP1 and DTP3 coverage and the percentage of districts with ≥ 90% and < 80% DTP3 coverage.ResultsFor 2010-19, 451 diphtheria cases were reported in the Region. DTP1 and DTP3 coverage was 92-96% and 95-97%, respectively. For 2019, 52 cases were reported by 11 of 48 countries that submitted reports (including zero reporting). Thirty-nine countries submitted data on percentage of their districts with ≥ 90% and < 80% DTP3 coverage; 26 had ≥ 90% districts with ≥ 90% coverage while 11 had 1-40% districts with < 80% coverage.ConclusionLong-standing high DTP3 coverage at Regional level probably explains the relatively few diphtheria cases reported in the Region. Suboptimal surveillance systems and inadequate laboratory diagnostic capacity may also be contributing factors. Still, the observed cases are of concern. Attaining high DTP3 coverage in all districts and implementing recommended booster doses are necessary to control diphtheria and prevent outbreaks.
Topics: Child; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Global Health; Humans; Immunization Programs; Infant; Vaccination; Vaccination Coverage; World Health Organization
PubMed: 35209973
DOI: 10.2807/1560-7917.ES.2022.27.8.2100058 -
Emerging Infectious Diseases Oct 2019In 2017, a total of 8,819 cases of diphtheria were reported worldwide, the most since 2004. However, recent diphtheria epidemiology has not been well described. We...
In 2017, a total of 8,819 cases of diphtheria were reported worldwide, the most since 2004. However, recent diphtheria epidemiology has not been well described. We analyzed incidence data and data from the literature to describe diphtheria epidemiology. World Health Organization surveillance data were 81% complete; completeness varied by region, indicating underreporting. As national diphtheria-tetanus-pertussis (DTP) 3 coverage increased, the proportion of case-patients <15 years of age decreased, indicating increased protection of young children. In countries with higher case counts, 66% of case-patients were unvaccinated and 63% were <15 years of age. In countries with sporadic cases, 32% of case-patients were unvaccinated and 66% were >15 years of age, consistent with waning vaccine immunity. Global DTP3 coverage is suboptimal. Attaining high DTP3 coverage and implementing recommended booster doses are necessary to decrease diphtheria incidence. Collection and use of data on subnational and booster dose coverage, enhanced laboratory capacity, and case-based surveillance would improve data quality.
Topics: Adolescent; Child; Child, Preschool; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Global Health; Humans; Incidence; Infant; Population Surveillance; Vaccination Coverage
PubMed: 31538559
DOI: 10.3201/eid2510.190271 -
Microbiology Spectrum Jul 2019Diphtheria is one of the most well studied of all the bacterial infectious diseases. These milestone studies of toxigenic along with its primary virulence determinant,... (Review)
Review
Diphtheria is one of the most well studied of all the bacterial infectious diseases. These milestone studies of toxigenic along with its primary virulence determinant, diphtheria toxin, have established the paradigm for the study of other related bacterial protein toxins. This review highlights those studies that have contributed to our current understanding of the structure-function relationships of diphtheria toxin, the molecular mechanism of its entry into the eukaryotic cell cytosol, the regulation of diphtheria expression by holo-DtxR, and the molecular basis of transition metal ion activation of apo-DtxR itself. These seminal studies have laid the foundation for the protein engineering of diphtheria toxin and the development of highly potent eukaryotic cell-surface receptor-targeted fusion protein toxins for the treatment of human diseases that range from T cell malignancies to steroid-resistant graft-versus-host disease to metastatic melanoma. This deeper scientific understanding of diphtheria toxin and the regulation of its expression have metamorphosed the third-most-potent bacterial toxin known into a life-saving targeted protein therapeutic, thereby at least partially fulfilling Paul Erlich's concept of a magic bullet-"a chemical that binds to and specifically kills microbes or tumor cells."
Topics: Animals; Bacterial Proteins; Corynebacterium diphtheriae; DNA-Binding Proteins; Diphtheria; Diphtheria Toxin; Gene Expression Regulation, Bacterial; Humans; Iron; Operon
PubMed: 31267892
DOI: 10.1128/microbiolspec.GPP3-0063-2019 -
Revista de Saude Publica Dec 2011The article is a literature review on the emergence of human infections caused by Corynebacterium ulcerans in many countries including Brazil. Articles in Medline/PubMed... (Review)
Review
The article is a literature review on the emergence of human infections caused by Corynebacterium ulcerans in many countries including Brazil. Articles in Medline/PubMed and SciELO databases published between 1926 and 2011 were reviewed, as well as articles and reports of the Brazilian Ministry of Health. It is presented a fast, cost-effective and easy to perform screening test for the presumptive diagnosis of C. ulcerans and C. diphtheriae infections in most Brazilian public and private laboratories. C. ulcerans spread in many countries and recent isolation of this pathogen in Rio de Janeiro, southeastern Brazil, is a warning to clinicians, veterinarians, and microbiologists on the occurrence of zoonotic diphtheria and C. ulcerans dissemination in urban and rural areas of Brazil and/or Latin America.
Topics: Animals; Brazil; Clinical Laboratory Techniques; Communicable Diseases, Emerging; Corynebacterium; Corynebacterium Infections; Corynebacterium diphtheriae; Diphtheria; Disease Notification; Epidemics; Global Health; Humans; Zoonoses
PubMed: 22124745
DOI: 10.1590/s0034-89102011000600021 -
The Lancet. Infectious Diseases Sep 2015We describe the case of a patient with cutaneous diphtheria caused by toxigenic Corynebacterium ulcerans who developed a right hand flexor sheath infection and symptoms... (Review)
Review
We describe the case of a patient with cutaneous diphtheria caused by toxigenic Corynebacterium ulcerans who developed a right hand flexor sheath infection and symptoms of sepsis such as fever, tachycardia, and elevated C-reactive protein, after contact with domestic cats and dogs, and a fox. We summarise the epidemiology, clinical presentation, microbiology, diagnosis, therapy, and public health aspects of this disease, with emphasis on improving recognition. In many European countries, C ulcerans has become the organism commonly associated with cutaneous diphtheria, usually seen as an imported tropical disease or resulting from contact with domestic and agricultural animals. Diagnosis relies on bacterial culture and confirmation of toxin production, with management requiring appropriate antimicrobial therapy and prompt administration of antitoxin, if necessary. Early diagnosis is essential for implementation of control measures and clear guidelines are needed to assist clinicians in managing clinical diphtheria. This case was a catalyst to the redrafting of the 2014 national UK interim guidelines for the public health management of diphtheria, released as final guidelines in March, 2015.
Topics: Aged; Corynebacterium; Diphtheria; Female; Hand Dermatoses; Humans; Skin Diseases, Bacterial
PubMed: 26189434
DOI: 10.1016/S1473-3099(15)00225-X -
Clinical Infectious Diseases : An... Oct 2021Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment...
BACKGROUND
Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment for diphtheria. The 2017-2018 outbreak among Rohingya refugees in Bangladesh was the largest in decades. We determined the outcomes of DAT-treated patients and describe the occurrence and risk factors associated with adverse reactions to DAT.
METHODS
We conducted a retrospective study at the Médecins Sans Frontières Rubber Garden Diphtheria Treatment Center from December 2017-September 2018. Diphtheria was diagnosed based on the World Health Organization clinical case criteria. High-acuity patients were eligible for DAT. Safety precautions were meticulously maintained. We calculated the presence of adverse events by age, duration of illness, and DAT dosage using bivariate comparisons.
RESULTS
We treated 709 patients with DAT; 98% (n = 696) recovered and were discharged. One-fourth (n = 170) had at least 1 adverse reaction. Common reactions included cough (n = 115, 16%), rash (n = 66, 9%), and itching (n = 37, 5%). Three percent (n = 18) had severe hypersensitivity reactions. Five patients died during their DAT infusion or soon afterwards, but no deaths were attributed to DAT.
CONCLUSIONS
Outcomes for DAT-treated patients were excellent; mortality was <1%. Adverse reactions occurred in one-quarter of all patients, but most reactions were mild and resolved quickly. DAT can be safely administered in a setting with basic critical care, provided there is continuous patient monitoring during the infusion, staff training on management of adverse effects, and attention to safety precautions.
Topics: Bangladesh; Diphtheria; Diphtheria Antitoxin; Disease Outbreaks; Humans; Retrospective Studies
PubMed: 33245364
DOI: 10.1093/cid/ciaa1718 -
Journal of Clinical Microbiology Nov 2021Corynebacterium diphtheriae is highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters...
Corynebacterium diphtheriae is highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters are observed in high-vaccination settings. The phylogeography and short timescale evolution of C. diphtheriae are not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking. We combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST gene diversity among 602 isolates from sporadic clinical cases, small clusters, or large outbreaks. We defined sublineages based on the phylogenetic structure within C. diphtheriae and strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages. The cgMLST scheme showed high allele call rate in C. diphtheriae and the closely related species C. belfantii and C. rouxii. We demonstrate its utility to delineate epidemiological case clusters and outbreaks using a 25 mismatches threshold and reveal a number of cryptic transmission chains, most of which are geographically restricted to one or a few adjacent countries. Subcultures of the vaccine strain PW8 differed by up to 20 cgMLST mismatches. Phylogenetic analyses revealed a short-timescale evolutionary gain or loss of the diphtheria toxin and biovar-associated genes. We devised a genomic taxonomy of strains and deeper sublineages (defined using a 500-cgMLST-mismatch threshold), currently comprising 151 sublineages, only a few of which are geographically widespread based on current sampling. The cgMLST genotyping tool and nomenclature was made publicly accessible (https://bigsdb.pasteur.fr/diphtheria). Standardized genome-scale strain genotyping will help tracing transmission and geographic spread of C. diphtheriae. The unified genomic taxonomy of C. diphtheriae strains provides a common language for studies of ecology, evolution, and virulence heterogeneity among C. diphtheriae sublineages.
Topics: Corynebacterium diphtheriae; Diphtheria; Genome, Bacterial; Genomics; Humans; Multilocus Sequence Typing; Phylogeny
PubMed: 34524891
DOI: 10.1128/JCM.01581-21 -
Epidemiology and Infection Jun 2018This research investigates the long-forgotten relationship between diphtheria and tuberculosis. Historical medical reports from the late 19th century are reviewed...
This research investigates the long-forgotten relationship between diphtheria and tuberculosis. Historical medical reports from the late 19th century are reviewed followed by a statistical regression analysis of the relationship between the two diseases in the early 20th century. Historical medical reports show a consistent association between diphtheria and tuberculosis that can increase the likelihood and severity of either disease in a co-infection. The statistical analysis uses historical weekly public health data on reported cases in five American cities over a period of several years, finding a modest but statistically significant relationship between the two diseases. No current medical theory explains the association between diphtheria and tuberculosis. Alternative explanations are explored with a focus on how the diseases assimilate iron. In a co-infection, the effectiveness of tuberculosis at assimilating extracellular iron may lead to increased production of diphtheria toxin, worsening that disease, which may, in turn, exacerbate tuberculosis. Iron-dependent repressor genes connect both diseases.
Topics: Cities; Diphtheria; History, 19th Century; History, 20th Century; Incidence; Tuberculosis; United States
PubMed: 29665871
DOI: 10.1017/S0950268818000936 -
Journal of Infection in Developing... Jun 2022Toxigenic Corynebacterium diphtheriae causes classical diphtheria. Skin infections by toxigenic or non-toxigenic Corynebacterium diphtheriae are prevalent in the tropics...
INTRODUCTION
Toxigenic Corynebacterium diphtheriae causes classical diphtheria. Skin infections by toxigenic or non-toxigenic Corynebacterium diphtheriae are prevalent in the tropics but are rarely reported.
CASE PRESENTATION
We report the identification of a non-toxigenic Corynebacterium diphtheriae (biovar Gravis) isolate in a 52-year-old Cambodian male. The patient presented purulent and non-healing ulcerations on the right hallux. The wound has healed after 7 days of antibiotic therapy with a favourable outcome.
CONCLUSIONS
This case represents, to our knowledge, the first report of Corynebacterium diphtheriae in Cambodia in the last 10 years, and highlights the lack of diagnosis and notifications of diphtheria. It is important to raise awareness among clinicians and to set up diphtheria surveillance in Cambodia.
Topics: Corynebacterium; Corynebacterium Infections; Corynebacterium diphtheriae; Diphtheria; Hallux; Humans; Male; Middle Aged
PubMed: 35797309
DOI: 10.3855/jidc.16153