Comunicação de risco: caso suspeito de difteria / Risk communication: suspected case of diphtheria

A comunicação de risco tem como objetivo apoiar na divulgação rápida e eficaz de conhecimento às populações, parceiros e partes intervenientes possibilitando o acesso às informações fidedignas que possam apoiar nos diálogos para tomada de medidas de proteção e controle em situações de emergência em saúde pública. Em Goiás na SE 16/2022, foi notificado 01 caso suspeito de difteria, sexo feminino, 16 anos, do município de Santa Helena de Goiás, com histórico de 03 doses da vacina DTP+HIB (08/2010), não foi identificada doses de reforço, conforme preconizados pelo PNI

Risk communication aims to support the rapid and effective dissemination of knowledge to populations, partners and stakeholders, enabling access to reliable information that can support dialogues for taking protection and control measures in emergency situations in public health. In Goiás on SE 16/2022, 01 suspected case of diphtheria was reported, female, 16 years old, from the municipality of Santa Helena de Goiás, with a history of 03 doses of the DTP+HIB vaccine (08/2010), no doses were identified reinforcement, as recommended by the PNI

Global Stability Analysis and Parameter Estimation for a Diphtheria Model: A Case Study of an Epidemic in Rohingya Refugee Camp in Bangladesh.

In this article, we have developed a deterministic Susceptible-Latent-Infectious-Recovered (SLIR) model for diphtheria outbreaks. Here, we have studied a case of the diphtheria outbreak in the Rohingya refugee camp in Bangladesh to trace the disease dynamics and find out the peak value of the infection. Both analytical and numerical investigations have been performed on the model to find several remarkable behaviors like the positive and bounded solution, basic reproductive ratio, and equilibria such as disease extinction equilibrium and disease persistence equilibrium which are characterized depending on the basic reproductive ratio and global stability of the model using Lyapunov function for both equilibria. Parameter estimation has been performed to determine the values of the parameter from the daily case data using numerical technique and determined the value of the basic reproductive number for the outbreak as ℛ 0 = 5.86.

Whole-Genome Sequencing of Corynebacterium diphtheriae Isolates Recovered from an Inner-City Population Demonstrates the Predominance of a Single Molecular Strain.

In some parts of the world, Corynebacterium diphtheriae has reemerged as a pathogen, especially as a cause of infections among impoverished and marginalized populations. We performed whole-genome sequencing (WGS) on all cutaneous C. diphtheriae isolates (n = 56) from Vancouver's inner-city population over a 3-year time period (2015 to 2018). All isolates with complete genome assembly were toxin negative, contained a common set of 22 virulence factors, and shared a highly conserved accessory genome. One of our isolates harbored a novel plasmid conferring macrolide and lincosamide resistance. Fifty-two out of 56 isolates were multilocus sequence type 76, and single nucleotide variants (SNV) and core-genome multilocus sequence typing (cgMLST) analysis demonstrated tight clustering of our isolates relative to all publicly available C. diphtheriae genomes. All sequence type 76 (ST76) study isolates were within a median of 22 SNVs and 13 cgMLST alleles of each other, while NCBI genomes were within a median of 17,436 SNVs and 1,552 cgMLST alleles of each other (both P < 2.2 × 10-16). A single strain of C. diphtheriae appears to be causing cutaneous infections in the low-income population of Vancouver. Further research is needed to elucidate transmission networks in our study population and standardize C. diphtheriae epidemiological typing when whole genomes are sequenced.

Talk to Patients About: Diphtheria.

Most people know little about diphtheria today thanks to the effectiveness of its vaccine. But fear of this highly contagious bacterial infection - which chokes off patients' ability to breathe - was once so strong that it accidentally gave birth to a major sporting event: the Iditarod Trail Dog Sled Race.

Risk of Measles and Diphtheria Introduction and Transmission on Bonaire, Caribbean Netherlands, 2018.

Endemic transmission of measles has been reestablished in Venezuela, and outbreaks of diphtheria remain ongoing across Latin America (LA). Hence, a large cross-sectional population-based serosurveillance study was conducted on Bonaire, one of the Dutch Leeward Antilles, to assess specific age and population groups at risk. Participants (aged 0-90 years) donated a blood sample and completed a questionnaire (n = 1,129). Antibodies against measles and diphtheria were tested using bead-based multiplex immunoassays. Our data revealed that immunity against measles is suboptimal, especially for those aged less than 5 years from Suriname, Aruba, and former Dutch Antilles (SADA), and adolescents from LA; and against diphtheria for persons aged more than 30 years, particularly among females and residents from SADA and LA. As refugees arrive persistently, health authorities on the Dutch Leeward Antilles should be on alert to detect early cases and prevent subsequent transmission. Ultimately, there is an urgent need for serosurveillance studies in the Caribbean region.

Carriage of a Single Strain of Nontoxigenic Corynebacterium diphtheriae bv. Belfanti (Corynebacterium belfantii) in Four Patients with Cystic Fibrosis.

Cystic fibrosis (CF) patients are commonly colonized by bacterial pathogens, which can induce persistent lung inflammation and may contribute to clinical deterioration. Colonization of CF patients and cross-transmission by Corynebacterium diphtheriae have not been reported so far. The aim of this article was to investigate the possibility of a cross-transmission of C. diphtheriae biovar Belfanti between four patients of a CF center. C. diphtheriae biovar Belfanti (now formally called C. belfantii) isolates were collected from four patients in a single CF care center over a period of 6 years and analyzed by microbiological methods and whole-genome sequencing. Epidemiological links among patients were investigated. Ten isolates were collected from 4 patients. Whole-genome sequencing of one isolate from each patient showed that a single strain was shared among them. In addition, one patient was found to have the same strain in two consecutive samplings performed 9 months apart. The strain was nontoxigenic and was susceptible to most antimicrobial agents. Ciprofloxacin resistance was observed in one patient. The idea of transmission of the strain among patients was supported by the occurrence of same-day visits to the CF center. This study demonstrated colonization of CF patients by C. diphtheriae biovar Belfanti (C. belfantii), and the data suggest persistence and transmission of a unique strain during at least 6 years in a single CF patient care center.

NGS-based phylogeny of diphtheria-related pathogenicity factors in different Corynebacterium spp. implies species-specific virulence transmission.

BACKGROUND: Diphtheria toxin (DT) is produced by toxigenic strains of the human pathogen Corynebacterium diphtheriae as well as zoonotic C. ulcerans and C. pseudotuberculosis. Toxigenic strains may cause severe respiratory diphtheria, myocarditis, neurological damage or cutaneous diphtheria. The DT encoding tox gene is located in a mobile genomic region and tox variability between C. diphtheriae and C. ulcerans has been postulated based on sequences of a few isolates. In contrast, species-specific sequence analysis of the diphtheria toxin repressor gene (dtxR), occurring both in toxigenic and non-toxigenic Corynebacterium species, has not been done yet. We used whole genome sequencing data from 91 toxigenic and 46 non-toxigenic isolates of different pathogenic Corynebacterium species of animal or human origin to elucidate differences in extracted DT, DtxR and tox-surrounding genetic elements by a phylogenetic analysis in a large sample set. RESULTS: Sequences of both DT and DtxR, extracted from whole genome sequencing data, could be classified in four distinct, nearly species-specific clades, corresponding to C. diphtheriae, C. pseudotuberculosis, C. ulcerans and atypical C. ulcerans from a non-toxigenic toxin gene-bearing wildlife cluster. Average amino acid similarities were above 99% for DT and DtxR within the four groups, but lower between them. For DT, subgroups below species level could be identified, correlating with different tox-comprising mobile genetic elements. In most C. diphtheriae, tox genes were located within known prophages. In contrast, in C. ulcerans diverse tox-including mobile elements could be identified: either prophages differing from C. diphtheriae prophages or an alternative pathogenicity island (PAI) described previously. One isolate showed a different, shorter tox-comprising putative PAI. Beyond the tox-overlapping elements, most isolates harbored a variety of additional prophages. CONCLUSION: Our NGS data from 137 isolates indicate the existence of different genetic backgrounds of DT-mediated pathogenicity in different Corynebacterium species and evolution of once acquired pathogenicity features with the strains. Different groups of pathogenicity-related elements within C. ulcerans imply that tox transmission pathways between isolates may differ in the zoonotic species and contribute to their emerging pathogenic potential.

Whole genome sequencing suggests transmission of Corynebacterium diphtheriae-caused cutaneous diphtheria in two siblings, Germany, 2018.

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child's sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae. Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.

Fatal Case of Diphtheria and Risk for Reemergence, Singapore.

We report a fatal autochthonous diphtheria case in a migrant worker in Singapore. This case highlights the risk for individual cases in undervaccinated subpopulations, despite high vaccination coverage in the general population. Prompt implementation of public health measures and maintaining immunization coverage are critical to prevent reemergence of diphtheria.

Validación de un ensayo inmunoenzimático tipo ELISA para cuantificar niveles de antitoxina diftérica en suero humano / Validation of an ELISA-type immune-enzymatic test to quantify levels of diphtheria antitoxin in human serum

Introducción: La difteria aún persiste en numerosos países. En Cuba, estudios realizados en diferentes grupos etarios han demostrado que existen niveles no protectores de antitoxina diftérica en la población, por lo que es necesario contar con métodos que permitan la estimación serológica de la inmunidad poblacional. La cuantificación de anticuerpos contra antígenos vacunales como la toxina diftérica es además un método útil, rápido y económico para evaluar la respuesta inmune. Objetivo: Validar un ensayo inmunoenzimático tipo ELISA para cuantificar los niveles de antitoxina diftérica en suero humano. Material y Método: Se realizó un estudio experimental de desarrollo tecnológico, en el cual se determinaron los valores óptimos de las variables que influyen en el resultado de un ensayo inmunoenzimático heterogéneo indirecto para la cuantificación de antitoxina diftérica, desarrollado en el laboratorio de Inmunología del Centro Nacional de Genética Médica de Cuba. La curva de calibración se evaluó contra el estándar de la OMS (Diphtheria Antitoxin Human Serum 00/496). Se realizó la validación analítica del método estandarizado. Resultados: Los coeficientes de variación intraensayo e interensayo fueron inferiores a 10 por ciento y 20 por ciento, respectivamente. En la exactitud y selectividad se encontraron valores de recobrado entre 90 y 110 por ciento. El paralelismo entre la curva estándar y las muestras estudiadas presentó un coeficiente de variación menor o igual a 10 por ciento. El límite de cuantificación fue 0,015 UI/mL y el de detección 0,0039 UI/mL. Conclusiones: El resultado obtenido en la precisión, exactitud y selectividad del ensayo inmunoenzimático tipo ELISA desarrollado demostró que puede ser utilizado en la práctica clínica para cuantificar los valores de antitoxina diftérica en suero humano(AU)

Introduction: Diphtheria still persists in many countries. In Cuba, studies conducted in different age groups have demonstrated that there are non-protective levels of diphtheria antitoxin in the population, so it is necessary to have methods that allow the serologic survey of population immunity. The quantification of antibodies against vaccine antigens such as diphtheria toxin is also a useful, rapid and economic method to evaluate the immune response. Objective: To validate an ELISA-type immune-enzymatic test to quantify the levels of diphtheria antitoxin in human serum. Material and Method: An experimental study of technological development was carried out in the Immunology Laboratory of the National Medical Genetics Center, Havana, Cuba. The optimal values ​​of the variables that influence on the result of the indirect heterogeneous immune-enzymatic test for the quantification of diphtheria antitoxin were determined. The calibration curve obtained was evaluated against the WHO standard (Diphtheria Antitoxin Human Serum 00/496). The analytical validation of the standardized method was performed. Results: The intra-assay and inter-assay coefficients of variation were less than 10 percent and 20 percent, respectively. Recovery values ​​between 90 and 110% were found in accuracy and selectivity. The parallelism between the standard curve and the samples studied showed a coefficient of variation lower or equal to 10 percent. The limit of quantification was 0,015 IU/mL and the one of detection was 0,0039 IU/mL. Conclusions: The result obtained in the precision, accuracy and selectivity of the ELISA-type immune-enzymatic test developed and validated in the National Medical Genetics Center demonstrated that it can be used in the clinical practice to quantify the values ​​of diphtheria antitoxin in human serum(AU)

Informe especial: Actualización epidemiológica de difteria / Special report: Epidemiological update of diphtheria

La difteria es una enfermedad infecciosa grave, con potencial epidémico, para la que existe una vacuna eficaz. Es una infección bacteriana aguda causada por la liberación de una exotoxina específica, producida por el bacilo gram positivo, Corynebacterium diphtheriae. Sólo las cepas toxigénicas causan enfermedad. La enfermedad se presenta principalmente en menores de 15 años de edad sin vacunación o con vacunación incompleta; no obstante puede presentarse en adultos en áreas con baja cobertura de vacunación. En este informe se presentan distintos aspectos de la enfermedad y la situación epidemiológica en las Américas y en Argentina: definiciones de caso, medidas de prevención y de control

Diphtheria in Mayotte, 2007-2015.

Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007-2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.

Mathematical modeling of diphtheria transmission in Thailand.

In this work, a mathematical model for describing diphtheria transmission in Thailand is proposed. Based on the course of diphtheria infection, the population is divided into 8 epidemiological classes, namely, susceptible, symptomatic infectious, asymptomatic infectious, carrier with full natural-acquired immunity, carrier with partial natural-acquired immunity, individual with full vaccine-induced immunity, and individual with partial vaccine-induced immunity. Parameter values in the model were either directly obtained from the literature, estimated from available data, or estimated by means of sensitivity analysis. Numerical solutions show that our model can correctly describe the decreasing trend of diphtheria cases in Thailand during the years 1977-2014. Furthermore, despite Thailand having high DTP vaccine coverage, our model predicts that there will be diphtheria outbreaks after the year 2014 due to waning immunity. Our model also suggests that providing booster doses to some susceptible individuals and those with partial immunity every 10 years is a potential way to inhibit future diphtheria outbreaks.

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans, with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery.

Evolution, epidemiology and diversity of Corynebacterium diphtheriae: New perspectives on an old foe.

Diphtheria is a debilitating disease caused by toxigenic Corynebacterium diphtheriae strains and has been effectively controlled by the toxoid vaccine, yet several recent outbreaks have been reported across the globe. Moreover, non-toxigenic C. diphtheriae strains are emerging as a major global health concern by causing severe pharyngitis and tonsillitis, endocarditis, septic arthritis and osteomyelitis. Molecular epidemiological investigations suggest the existence of outbreak-associated clones with multiple genotypes circulating around the world. Evolution and pathogenesis appears to be driven by recombination as major virulence factors, including the tox gene and pilus gene clusters, are found within genomic islands that appear to be mobile between strains. The number of pilus gene clusters and variation introduced by gain or loss of gene function correlate with the variable adhesive and invasive properties of C. diphtheriae strains. Genomic variation does not support the separation of C. diphtheriae strains into biovars which correlates well with findings of studies based on multilocus sequence typing. Genomic analyses of a relatively small number of strains also revealed a recombination driven diversification of strains within a sequence type and indicate a wider diversity among C. diphtheriae strains than previously appreciated. This suggests that there is a need for increased effort from the scientific community to study C. diphtheriae to help understand the genomic diversity and pathogenicity within the population of this important human pathogen.

Colonisation with toxigenic Corynebacterium diphtheriae in a Scottish burns patient, June 2015.

On 12 June 2015, Corynebacterium diphtheriae was identified in a skin swab from a burns patient in Scotland. The isolate was confirmed to be genotypically and phenotypically toxigenic. Multilocus sequence typing of three patient isolates yielded sequence type ST 125. The patient was clinically well. We summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for C. diphtheriae.

Possible human-to-human transmission of toxigenic Corynebacterium ulcerans.

Toxigenic Corynebacterium ulcerans is an emerging cause of diphtheria. In contrast to the classical diphtheria pathogen C. diphtheriae, human-to-human transmission of this primarily zoonotic pathogen has not been clearly documented. Here we report on a two-person cluster suggesting an initial zoonotic and a subsequent human-to-human transmission event.

Corynebacterium species nasal carriage in pigs and their farmers in Bavaria, Germany: implications for public health.

Reports on cases of human diphtheria caused by toxigenic Corynebacterium ulcerans that were linked to occupational swine contact as well as isolation of C ulcerans from wild boars have suggested that pigs might serve as reservoir for human infections. Therefore, a prevalence study on Corynebacterium species nasal carriage in pigs and their farmers was performed between August 1 and December 31, 2009, in 41 swine farms from Bavaria, Germany. All 411 asymptomatic pigs and 29 of 30 healthy farmers were colonised with Corynebacterium strains of up to 11 different species. No potentially toxigenic Corynebacterium strain was isolated either from the pigs or from their farmers, respectively. The patterns of the species composition in the pigs and the farmers were very similar, suggesting a potential transmission of strains between animals and humans.