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1
Spinler, Jennifer K. "Characterizing the diphtheria-toxin-repressor (DtxR) regulon in Corynebacterium diphtheriae /". Connect to full text via ProQuest. IP filtered, 2006.
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Thesis (Ph.D. in Microbiology) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 142-160). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
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Хілько, Артем Сергійович, Артем Сергеевич Хилько, Artem Serhiiovych Khilko, Оксана Миколаївна Чемич, Оксана Николаевна Чемич, Oksana Mykolaivna Chemych, Микола Дмитрович Чемич, Николай Дмитриевич Чемич i Mykola Dmytrovych Chemych. "Clinical and epidemiological features of diphtheria". Thesis, Видавництво СумДУ, 2010. http://essuir.sumdu.edu.ua/handle/123456789/6751.
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Wagner, Karen Susan. "Diphtheria epidemiology in the UK and Europe". Thesis, Manchester Metropolitan University, 2015. http://e-space.mmu.ac.uk/25/.
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A resurgence of diphtheria (Corynebacterium diphtheriae) occurred in the former Soviet Union in the 1990s. Concerted control measures brought about a decline in cases, however some endemic transmission has continued and increasingly C. ulcerans cases have been reported in some Western European countries. Questions existed regarding risk factors for infection, availability of diphtheria antitoxin (DAT) treatment, circulation of potentially toxigenic Corynebacteria, and UK population immunity. Surveillance data from the World Health Organization European Region, Diphtheria Surveillance Network (DIPNET) and UK were analysed. In addition, 47 countries provided information regarding their DAT treatment supplies. To examine circulation of Corynebacteria, throat swabs were screened across ten countries. UK diphtheria immunity was assessed by serosurvey, and vaccination coverage data from nine London Primary Care Trusts (PCTs) were analysed by ethnicity. During 2000-2009 C. diphtheriae cases declined across the European Region. C. ulcerans cases (associated with domestic animals) outnumbered C. diphtheriae (associated with travel to endemic areas) in DIPNET countries outside the former Soviet Union. There was a clear protective effect of vaccination. The case fatality rate for respiratory diphtheria was lower in Latvia than in other DIPNET countries. Global shortages of DAT were highlighted. Screening identified endemic transmission of toxigenic C. diphtheriae in Latvia and Lithuania, and circulation of non-toxigenic strains in several countries. UK population immunity had increased since the last serosurvey in 1996; in 2009 75% of the population had at least basic protection. Low childhood vaccination coverage in London related partly to the size of ethnic groups within a PCT but also to completeness of data records. Surveillance and screening datasets likely missed some cases/isolates due to lost clinical and/or laboratory expertise. These skills need to be retained and high vaccination coverage levels achieved, as well as records accurately maintained. A DAT alternative is needed, with improved availability and access.
4
Wenzel, Esther Veronika Verfasser], Michael [Akademischer Betreuer] [Hust i Stefan [Akademischer Betreuer] Dübel. "Development of recombinant human anti-diphtheria toxin neutralizing antibodies for diphtheria therapy / Esther Veronika Wenzel ; Michael Hust, Stefan Dübel". Braunschweig : Technische Universität Braunschweig, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:084-2019050215003.
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Красовицький, Зіновій Йосипович, Зиновий Иосифович Красовицкий, Zinovii Yosypovych Krasovytskyi, Андрій Олегович Сніцар, Андрей Олегович Сницарь, Andrii Olehovych Snitsar i В. В. Минаков. "К вопросу диагностики "современной" дифтерии". Thesis, Издательство СумГУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24744.
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Васильєв, Юрій Костянтинович, Юрий Константинович Васильев, Yurii Kostiantynovych Vasyliev, Костянтин Костянтинович Васильєв, Константин Константинович Васильев i Kostiantyn Kostiantynovych Vasyliev. "Сезонные колебания в заболеваемости дифтерией в Сумской области в 1990-х годах". Thesis, Изд-во СумГУ, 2007. http://essuir.sumdu.edu.ua/handle/123456789/5274.
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Печінка, А. М. "Організаційний алгоритм надавання медичної допомоги хворим на тяжкі форми дифтерії". Thesis, Видавництво СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/11230.
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Було проведено аналіз 216 випадків смерті дорослих від дифтерії в різних регіонах України. У 121 випадків (56 %) мали місце серйозні організаційні недоліки, які вплинули на кінцевий наслідок захворювання. Це свідчить про необхідність чіткої організації надавання допомоги таким хворим, у зв’язку з чим нами був створений алгоритм надавання медичної допомоги хворим на тяжкі форми дифтерії.
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Чемич, Микола Дмитрович, Николай Дмитриевич Чемич, Mykola Dmytrovych Chemych, Юрій Костянтинович Васильєв, Юрий Константинович Васильев i Yurii Kostiantynovych Vasyliev. "Еволюція епідеміологічних особливостей дифтерії". Thesis, Вид-во СумДУ, 2006. http://essuir.sumdu.edu.ua/handle/123456789/6136.
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Каплін, Микола Микитович, Николай Никитович Каплин, Mykola Mykytovych Kaplin, Тетяна Сергіївна Габелюк, Татьяна Сергеевна Габелюк, Tetiana Serhiivna Habeliuk, Галина Іванівна Христенко i in. "Показатели антитоксического иммунитета у больных дифтерией". Thesis, Издательство СумГУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24816.
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Васильєв, Костянтин Костянтинович, Константин Константинович Васильев, Kostiantyn Kostiantynovych Vasyliev, Юрій Костянтинович Васильєв, Юрий Константинович Васильев i Yurii Kostiantynovych Vasyliev. "Я.Ю. Бардаха (1857-1929): исследования по серопрофилактике дифтерии". Thesis, Изд-во СумГУ, 2006. http://essuir.sumdu.edu.ua/handle/123456789/7899.
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Климовець, М. М., i Ю. В. Буряк. "Епідеміологічна ситуація щодо дифтерії в м. Суми та Сумській області". Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32278.
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Щорічно біля 500 тисяч людей в Україні хворіють на керовані інфекції. Більшість із них складають діти. У 80 роки XX ст. щороку хворіли на дифтерію близько 100 тис. людей, у 90-х роках – 19 тис. У цілому під час епідемії на території колишнього Радянського Союзу було зареєстровано 158 тис. випадків дифтерії та 4 тис. смертей. Обов’язкові щеплення проти цього захворювання знизили кількість випадків на дифтерію в Україні та у всьому світі більше ніж на 95%. Основною причиною епідемії була відсутність планової ревакцинації дорослого населення та збільшення кількості відмов батьків від імунізації дітей під впливом дискусії щодо шкоди щеплень. Додаткова масова імунізація проти дифтерії сприяла зниженню захворюваності на дифтерію за 7 років (1995-2002 р.р.) у 18 разів, токсигенного носійства – у 23 рази, показників смертності – у 20 разів.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/32278
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Троцька, І. А., Л. П. Куліш i Є. Г. Альперн. "Клініко-епідеміологічні особливості дифтерії в Сумській області". Thesis, Видавництво СумДУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24740.
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Федоренко, С. М., i Н. О. Тімко. "Епідситуація щодо захворюваності на дифтерію у Львівській області". Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32332.
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У Львівській області впродовж 2008 – 2013 років захворюваність на дифтерію реєструвалася наступним чином: в 2008 році зареєстровано 11 випадків з інтенсивним показником 0,43 проти 31 випадку з інтенсивним показником 0,13 в Україні.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/32332
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Федоренко, Ю. В., i В. С. Пінчук. "Ретроспективний погляд на епідемію дифтерії". Thesis, Видавництво СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/4798.
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Метою роботи було вивчення клініко-епідеміологічних особливостей дифтерії в умовах Північно-східного, прикордонного регіону України.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/4798
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Красовицький, Зіновій Йосипович, Зиновий Иосифович Красовицкий, Zinovii Yosypovych Krasovytskyi, Лариса Петрівна Кулеш, Лариса Петровна Кулеш, Larysa Petrivna Kulesh, В. Н. Демьяненко, П. С. Праведная i В. В. Иванов. "Особенности клинического течения дифтерии в последние годы". Thesis, Издательство СумГУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24768.
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Revenko, G. O., V. V. Mavrutenkov i Z. O. Chykarenko. "Strength of population immunity against diphtheria in Dnipropetrovs'k region". Thesis, Sumy State University, 2017. http://essuir.sumdu.edu.ua/handle/123456789/64773.
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Встановлено, що рівень протективного імунітету
проти дифтерії становив 69,5%. Переконливий рівень
імунологічного захисту серед дітей становив 70,9%, серед
дорослих – 68,3%. Жодна з вікових груп не мала достатнього
рівня антитоксичного імунітету, необхідного для припинення
трансмісії збудника дифтерії. Відсоток захищених осіб
знижувався зі збільшенням віку людей. Така ситуація може
створювати передумови для спалахів дифтерії у
Дніпропетровській області.Diphtheria is an infectious disease spread of which is limited by population post-vaccination immunity. In the system of epidemiological surveillance of diphtheria for objective assessment and prediction of epidemic situation in low intensity of epidemic process of this infection the serological control of immunity is crucial.
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Bass, Allan G. "The diphtheria epidemic in the Republic of Moldova 1994-1996 and its control /". [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18699.pdf.
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Nascimento, Dilzamar Veloso do. "Construção, clonagem e expressão do fragmento B da toxina diftérica de Corynebacterium diphtheriae (cepa PW- 8) em Mycobacterium bovis BCG sub-cepa Moreau". Universidade do Estado do Rio de Janeiro, 2014. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=9023.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA vacina anti-diftérica de uso corrente no Brasil (DTP), embora de alta eficácia na prevenção da difteria, está associada com episódios de toxicidade e reatogenicidade no recipiente vacinal, resultantes de proteínas residuais derivadas do processo de produção ou detoxificação. Estratégias para o desenvolvimento de vacinas menos reatogênicas e ao mesmo tempo mais eficazes e economicamente viáveis contra a difteria têm sido alvo de intensa investigação. A alternativa proposta por nosso grupo é a utilização da vacina contra a tuberculose (Mycobacterium bovis BCG sub-cepa Moreau), como vetor do gene que codifica o fragmento B da toxina diftérica (dtb) de 58,3 kDa. Neste trabalho o dtb foi clonado no vetor micobacteriano bifuncional (pUS977) de expressão citoplasmática e os clones recombinantes (pUS977dtbPW8), após a transformação do BCG, foram testados com relação a expressão do DTB em BCG e quanto a antigenicidade frente a anticorpos policlonais anti-toxóide diftérico por Immunobloting. A integridade do gene dtb e a identidade das sequências de DNA da construção plasmidial pUS977dtbPW8 foram confirmadas por sequenciamento de DNA e análise de similaridade. A imunogenicidade do BCGr pUS977dtbPW8 expressando o DTB foi investigada em camundongos BALB/c, os resultados obtidos revelaram uma soroconversão específica (IgG). A infectividade e atividade microbicida do BCGr pUS977dtbPW8 no ambiente intracelular foi avaliada através da infecção de linhagens de células de monócitos humano (THP-1), os dados obtidos indicaram que houve sobrevivência intracelular em até 12 dias. Nesse contexto, esplenócitos dos camundongos imunizados com 30 e 60 dias foram extraídos, mostrando que o BCGr pUS977dtbPW8 persistiu até 60 dias na ausência de pressão seletiva e a viabilidade celular não sofreu alteração significativa durante o período testado. Por outro lado, o BCGr pUS977dtbPW8, quando submetido a seis sub-cultivos consecutivos in vitro não apresentou diferença significativa na capacidade de expressar o DTB, demonstrando portanto a persistência da estabilidade funcional da linhagem recombinante. A estabilidade estrutural da construção pUS977dtbPW8 também foi avaliada por PCR confirmando a presença do gene dtb em colônias do BCGr pUS977dtbPW8 . Adicionalmente, foi possível avaliar preliminarmente in vitro a capacidade soroneutralizante dos soros de camundongos imunizados com BCGr pUS977dtbPW8 após 30 e 60 dias em células VERO. A ação citotóxica da toxina diftérica entre as diluições de 1/4 e 1/16 foram neutralizadas com o pool de soros imunes com 60 dias. Finalmente, em nosso estudo foi possível avaliar o potencial da vacina BCG como vetor de expressão de um antígeno de Corynebacterium diphtheriae in vitro e in vivo.
The diphtheria vaccine currently used in Brazil (DTP), despite its history of high efficacy in the prevention of diphtheria, is associated with episodes of toxicity and vaccine reactogenicity in the vaccinee, resulting from the presence in the vaccine of residual proteins derived from the production process or detoxification. Strategies for the development of new vaccines more effective and economically viable against diphtheria have been the subject of intense investigation. The alternative proposed by our group is the use of the vaccine against tuberculosis (Mycobacterium bovis BCG Moreau sub strain) as a vector for the gene that encodes the 58.3 kDa fragment B of the diphtheria toxin (DTB). In our project the dtb gene was cloned into the bifunctional vector pUS977 for cytoplasmic expression and recombinant BCG (rBCG) clones, selected after transformation of BCG, were tested for expression of the DTB polypeptide and antigenicity against polyclonal antibodies anti- diphtheria toxoid by immunoblotting. The integrity and identity of the DNA sequence encoding the dtb gene carried by the plasmid construct pUS977dtbPW8 was confirmed by DNA Sequencing and Analysis of Similarity. The immunogenicity of the rBCG expressing the DTB was investigated in BALB/c mice and the results revealed a specific seroconversion (IgG). Also, infectivity and microbicidal activity were analyzed in the intracellular environment by infecting human monocytes (THP-1 cell line) with rBCG. The data obtained indicated intracellular survival within 12 days. In this context, splenocytes collected from mice at days 30 and 60 after immunization were removed and assayed for live bacteria. The results showed that rBCG persisted viable up to 60 days in the absence of selective pressure and cell viable counts did not change significantly during testing. Additionally, the rBCG subjected to six consecutive sub-cultures in vitro showed no significant difference in the ability to express the DTB, thus demonstrating the functional stability of the recombinant vaccine. The structural stability of the construct pUS977dtbPW8 was also confirmed by PCR detection of the dtb gene in rBCG colonies. Also, it was possible to have a preliminary evaluation of the neutralizing capacity of sera from mice immunized with BCGr 30 and 60 days after immunization. The cytotoxic action of diphtheria toxin, between dilutions 1/ 4 and 1/16, was neutralized by mice sera in an in vitro assay using VERO cells. Finally, in our study it was possible to evaluate the potential of BCG as a vector for expression of an antigen of Corynebacterium diphtheriae in vitro and in vivo.
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Peixoto, Renata Stavracakis. "Influência de pré-tratamentos de células epiteliais com penicilina e eritromicina na aderência e na viabilidade intracelular de Corynebacterium diphtheriae". Universidade do Estado do Rio de Janeiro, 2012. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=4446.
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Fundação de Amparo à Pesquisa do Estado do Rio de JaneiroA difteria é uma síndrome toxêmica causada pelo Corynebacterium diphtheriae. Embora programas de imunização mantenham a doença sob controle em países desenvolvidos, a difteria ainda permanece endêmica em diversas partes do mundo, especialmente em indivíduos parcialmente imunizados para toxina diftérica. Junto a isso, nos últimos 20 anos, tem-se observado a ocorrência crescente de quadros de infecções sistêmicas causados por cepas atoxinogênicas. A penicilina e eritromicina são as principais drogas de escolha no tratamento destas infecções, entretanto, a escassez de trabalhos reavaliando a terapia de escolha e a influência dos antibióticos no processo de interação bacteriana com células epiteliais humanas são escassos, logo compreendem aspectos que justificam o presente estudo. O objetivo principal deste projeto consiste na análise da influência do pré-tratamento de células epiteliais Hep-2 com os antimicrobianos penicilina e eritromicina na colonização e viabilidade intracelular de amostras de C. diphtheriae. As monocamadas foram submetidas ao tratamento prévio com doses séricas terapêuticas de penicilina (5g mL1) e eritromicina (1,92 g mL1) por 24 horas e os antibióticos foram removidos por lavagens com PBS antes da interação com a suspensão bacteriana (MOI de 107). Três horas após a infecção, o padrão de aderência foi investigado como também, realizada a análise das bactérias viáveis associadas e internalizadas nas monocamadas. O pré-tratamento com penicilina induziu a formação de perfil de aderência difuso (AD) pelas amostras estudadas. Microorganismos que normalmente apresentam padrão de aderência localizado (AL) passaram a expressar perfil (AD) após pré-tratamento das camadas com ambos antimicrobianos. A expressão do tipo agregativo (AA) não foi influenciada pela presença de eritromicina. A penicilina e a eritromicina reduziram o número de bactérias viáveis associadas às células HEp-2 na maioria das oportunidades. Entretanto, a penicilina interferiu em maior magnitude nesse processo. As três amostras invasoras de C. diphtheriae (HC01, HC04 e BR5015), apresentaram maior capacidade de sobrevivência no compartimento intracelular, independente do pré-tratamento. A expressão dos perfis de aderência assim como a capacidade de sobrevivência no compartimento intracelular frente aos antimicrobianos testados mostraram-se independentes da produção de toxina e dos percentuais de associação com as células HEp-2. Foi observada uma maior eficiência da eritromicina na eliminação de bactérias viáveis internalizadas reforçando a utilização clínica da eritromicina tanto no tratamento de pacientes quanto na erradicação do estado de portador. Novos estudos serão desenvolvidos para investigar alterações na expressão de fatores de virulência por amostras de C. diphtheriae na interação com células HEp-2 pré-tratadas com antimicrobianos e a influência sobre a evolução clínica das infecções por corinebactérias
Diphtheria is a syndrome caused by Toxigenic Corynebacterium diphtheriae. Although immunization programs have kept diphtheria under control in the great majority of developed countries, the disease remains endemic in many parts of the world, especially in individuals partially immunized to diphtheria toxoid. Additionally, an increase in the number of cases of systemic infections caused by non-toxigenic strains has been observed along the last 20 years. Penicillin and erythromycin have long been the drugs of choice for the treatment of C. diphtheriae infections, though the studies reviewing the choice of treatment and the influence of antibiotics in the process of bacterial interaction with human epithelial cells are scarce, and comprise the aspects that justify the present investigation. The main objective was to analyze the influence of pre-treatment of HEp-2 epithelial cells with the penicillin and erythromycin in adherence and intracellular viability of C. diphtheriae strains. HEp-2 monolayers were pre-treated for 24 hours with the serum concentration doses of penicillin (5g mL-1) and erythromycin (1.92 mg mL-1), and antibiotics were removed by washing with PBS before infection with bacterial suspension (MOI of 107). Three hours post-infection, the adherence pattern was investigated, and both percentage of viable cell-associated bacteria and intracellular bacteria was determined. Penicillin treatment induced the bacterial strains to exhibit diffuse adherence patterns (DA). Microorganisms that usually express localized adherence patterns (LA) began to express DA pattern after pre-treatment of monolayers with both antibiotics. Erythromycin did not influence the aggregative adherence pattern (AA). Penicillin and erythromycin reduced the number of viable HEp-2 cell-associated bacteria for the most of the strains. However, penicillin interfered in this process in a greater magnitude. The C. diphtheriae invasive strains (HC01, HC04 and BR5015) showed higher ability to survive within the intracellular compartment, regardless of pre-treatment. The expression of adherence patterns as well as the ability to survive in the intracellular environment of pre-treated cells, proved to be independent of toxin production and the usual percentage of association with HEp-2 cells. A higher efficiency in the reduction of intracellular viability with the use of erythromycin was observed for the majority of strains, and reinforces the clinical use of erythromycin in the treatment of patients alongside the eradication of the carrier state. Further studies will be necessary to investigate the changes in the expression of virulence factors in C. diphtheriae during the interaction with HEp-2 cells pre-treated with antimicrobials and the influence on the clinical evolution of corynebacterial infections
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Weissmueller, Nikolas T. "Needle-free vaccination : formulation and dermal delivery of diphtheria toxin CRM197 mutant". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:be74f39b-1f36-451c-8200-4f14b701bcee.
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The unsafe use of needles propagates cross infections with bloodborne pathogens and reduces the positive impact of vaccinations on global health. While a plethora of needle-free injection devices exist, the reformulation of protein-based vaccines is largely empirical and costly, which presents a barrier to their widespread clinical application. This thesis contributes to the identification of approaches that facilitate rapid vaccine reformulation and enhance the immunogenicity of needle-free dry-powder vaccines with the help of novel antigen delivery platforms. We hypothesised that the thermodynamic stabilisation of diphtheria toxin mutant 197 (CRM197), a glycoconjugate vaccine carrier protein, may enhance its structural preservation during spray-freeze-drying (SFD), and that its formulation in either soluble, surface-adsorbed, or nanoparticle form impacts the elicited immune response. Differential scanning fluorimetry was used to study the effect of excipients on the thermal stability of CRM197. Dry-powder formulation of CRM197 used i) encapsulation into a thermodynamically stabilising excipient matrix by SFD, ii) surface-immobilisation via physisorption onto a novel potassium-doped hydroxyapatite (kHA) carrier microparticle formed by molten salt synthesis, and iii) chemical conjugation and surface presentation on amphiphilic block copolymer nanoparticles that were incorporated into SFD-powders (SFD-NP). The structural integrity of CRM197 was assessed by size separation in addition to various spectral and thermal analysis methods. The immunogenicity of dry-powder CRM197 formulations was subsequently tested in vivo. The results suggest that the thermodynamic stability of CRM197 in solution does not ensure its structural stability during SFD. While needle-free dermal vaccination with kHA-adsorbed CRM197 induced comparable antibody titres to conventional IM injection of alum-adjuvanted CRM197, needle-free SFD and SFD-NP powders were less immunogenic. The highest mean IgG titre and most balanced Th1/Th2 response was achieved with nanoparticle-conjugated CRM197 by IM, which outperformed the current clinical standard. Therefore, future vaccine design should combine thermodynamic and kinetic stability screening, and place special emphasis on the delivery and structural presentation of the antigen to the immune system.
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Каплін, Микола Микитович, Николай Никитович Каплин, Mykola Mykytovych Kaplin i В. М. Ломко. "Характеристика антитоксичного імунітету у хворих на дифтерію в період спаду епідемії та роль вакцінації". Thesis, Видавництво СумДУ, 2003. http://essuir.sumdu.edu.ua/handle/123456789/8594.
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Христенко, Галина Іванівна, Галина Ивановна Христенко, Halyna Ivanivna Khrystenko, Тетяна Сергіївна Габелюк, Татьяна Сергеевна Габелюк, Tetiana Serhiivna Habeliuk i О. М. Черняк. "Особливості епідпроцесу при дифтерії в умовах епідеміологічної захворюваності і роль масової імунізації в її зниженні". Thesis, Видавництво СумДУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24733.
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Красовицький, Зіновій Йосипович, Зиновий Иосифович Красовицкий, Zinovii Yosypovych Krasovytskyi, Е. Г. Альперн i В. В. Шаповал. "Почему иммунизация населения против дифтерии проводимая в последние годы не дала ожидаемого эффекта". Thesis, Издательство СумГУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24712.
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Бинда, Тетяна Парфеніївна, Татьяна Парфеньевна Бында, Tetiana Parfeniivna Bynda, Олена Валентинівна Маркевич, Елена Валентиновна Маркевич, Olena Valentynivna Markevych, В. В. Тіщенко i С. Л. Грабовий. "Стан популяційного протидифтерійного антитоксичного імунітету в населення Сумської області". Thesis, Вид-во СумДУ, 2007. http://essuir.sumdu.edu.ua/handle/123456789/5744.
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Необхідними умовами оптимізації епідеміологічного нагляду за дифтерійною інфекцією є проведення імунологічного моніторингу, який дає можливість отримати інформацію про реальну захищеність населення від дифтерії і прийняти своєчасне та адекватне управлінське рішення, яке спрямоване на підвищення популяційного імунітету і зниження захворюваності дифтерією.
Метою роботи було оцінити стан популяційного протидифтерійного антитоксичного імунітету і рівень захищеності проти дифтерії населення Сумської області у 2006 р.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/5744
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Leka, Oneda. "Structural and functional characterization of A-B toxins: diphtheria toxin and clostridial neurotoxins". Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3421803.
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I performed my doctorate research activity studying three important human pathogens that are A-B toxins: Diphtheria Toxin (DT), Tetanus Neurotoxin (TeNT) and Botulinum neurotoxins (BoNTs), the etiologic agents of diphtheria, tetanus and botulism respectively. In terms of structural organization these toxins consist of three domains, which are termed L chain (the N-terminal catalytic domain), HN (the transmembrane domain), and HC (the C-terminal binding domain). These domains are closely related to the common four step mechanism of action: membrane binding mediated by HC, endocytosis, membrane translocation mediated by HN and L-chain mediated substrate modification.
I studied the conformational change of diphtheria toxin at acidic pH. DT includes a T domain which is known to mediate the pH-dependent membrane translocation, by forming a channel through which the catalytic domain crosses the endocytic vesicle membrane. To date no structural data are available about the pore/channel formed by the T domain, nor is known if it is monomeric or oligomeric. I have performed biochemical and structural studies to characterize the T domain of DT. The T domain is also considered a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to cancer cells. I obtained the crystal structure of DT in the presence of lipid bicelles (which simulate the endocytic vesicle membrane) and grown at pH 5.5, pH that mimics the acidic environment where translocation takes place. The reported structure throws lights on the initial event of this process, the destabilization of the three α-helices present at the bottom of the toxin (Leka et al., 2014).
I then worked on a project which aimed to unravel the three dimensional structure of tetanus neurotoxin by crystallization studies. Because TeNT is considered “uncrystallizable” I focused on the use of antibody fragments (Fabs) as crystallization chaperons to aid the structural determination. Native gel analysis and size exclusion chromatography showed the formation of a stable complex in vitro between TeNT and the relative Fabs. Several crystallization experiments were carried out by high throughput crystallization screens.
Further, I performed functional analysis on the trafficking of botulinum neurotoxin at the neuromuscular junction (NMJ). I expressed the binding domains of different BoNT serotypes, which are both necessary and sufficient for binding to the neuronal surface and internalization. The two step purifications, chromatography and gel filtration, were sufficient to yield purifications of each binding domain to >90% purity. Using cerebellum granular neurons (CGNs), I tested their functionality and specificity. I performed also in vivo assays in order to analyze their distribution along the NMJ. The data from fluorescence analysis show high specificity of these binding domains at the NMJ, and a different staining between different BoNT serotypes, reflecting their different time of intoxication, and perhaps a different pathway of vesicular trafficking.Ho effettuato la mia attività di ricerca studiando tre importanti patogeni umani, che sono tossine di tipo A-B: la tossina difterica (DT), la neurotossina tetanica (TeNT) e le neurotossine botuliniche (BoNTs), gli agenti eziologici di difterite, tetano e botulismo, rispettivamente. In termini di organizzazione strutturale queste tossine sono costituite da tre domini: il dominio catalitico (LH), il dominio di translocazione (HN) e il dominio di legame (HC). Questa organizzazione dei domini è strettamente correlata al loro comune meccanismo d’azione che comprende: il legame alla membrane cellulare mediato dal HC, la traslocazione del dominio catalitico nel citoplasma mediata dal canale di permeazione formato dal HN. Ho studiato il cambiamento conformazionale della tossina difterica a pH acido. DT include un dominio di translocazione (dominio T), che forma il canale attraverso il quale il dominio catalitico attraversa la membrana della vescicola endosomica. Fino ad oggi non ci sono dati strutturali che riguardano il canale formato dal dominio T, non si sa neanche se è un monomero o oligomero. Ho eseguito studi biochimici e strutturali per caratterizzare il dominio T di DT. Il dominio T è anche considerato un agente anti-cancro nelle terapie mirate contro le cellule tumorali. Ho ottenuto la struttura tridimensionale della tossina difterica in presenza di doppi strati lipidici (che simulano la membrana della vescicola endosomica) ed in condizioni di pH 5,5 (pH corrispondente all'ambiente acido in cui avviene la il processo di traslocazione). La struttura riportata getta luci sull'evento iniziale di questo processo, la destabilizzazione di tre alfa-eliche presenti nella parte inferiore della tossina (Leka et al., 2014). Ho poi lavorato su un progetto che mirava a caratterizzare la struttura tridimensionale della tosssina tetanica. Poiché la cristallizzazione di questa tossina risulta d’essere molto difficile, mi sono concentrata sull'utilizzo di frammenti di anticorpi (Fab) come tools per aiutare la determinazione strutturale. Analisi da gel nativo e da cromatografia ad esclusione mostrano la formazione di un complesso stabile in vitro tra la tossina ed i relativi Fab. Diversi esperimenti di cristallizzazione sono stati eseguiti, e per il momento non abbiamo ancora informazioni strutturali sulla tossina. Inoltre, ho studiato anche la localizzazione ed il processo di internalizzazione delle tossine botuliniche a livello della giunzione neuromuscolare (NMJ). Ho espresso i domini di legame di diversi sierotipi di tossine botuliniche, domini che sono necessari e sufficienti per il legame alla superficie dei neuroni. I domini di legame sono stati purificati utilizzando cromatografia di affinità e per esclusione, ottendo alla fine una purezza > 90% . Utilizzando i neuroni granulari di cervelletto (CGN), ho testato la loro funzionalità e specificità. Questi domini sono stati iniettati in vivo al fine di analizzare la loro localizzazione a livello della giunzione neuromuscolare. I dati ottenuti con analisi di microscopia confocale ed a fluorescenza mostrano che questi domini si localizzano proprio a livello della giunzione muscolare. Nelle marcature si osserva anche una colorazione diversa tra i diversi sierotipi BoNT, e questo risultato riflette il diverso tempo di intossicazione tra i vari serotipi di tossine botuliniche, e forse anche una diversa localizzazione in diverse vescicole endosomiche.
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Sabbadini, Priscila Soares. "Papel das hemaglutininas 67-72p de Corynebacterium diphtheriae na ligação a proteínas plasmáticas, superfícies celulares, invasão e indução de apoptose". Universidade do Estado do Rio de Janeiro, 2010. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=3591.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCorynebacterium diphtheriae pode ser isolado tanto de quadros de difteria clássica, quanto de infecções sistêmicas, como endocardite. O fibrinogênio (Fbn) e a fibronectina (Fn) são glicoproteínas presentes na matriz extracelular de tecidos conjuntivos. A influência destas proteínas na patogênese das infecções locais e invasivas causadas por C. diphtheriae é objeto de estudo devido ao fato do bacilo diftérico poder ser encontrado em lesões nas quais o Fbn e a Fn são predominantes, incluindo a pseudomembrana diftérica e vegetações cardíacas presentes na endocardite infecciosa. São crescentes as evidências de que o C. diphtheriae pode, além de aderir, ser internalizado por células em cultura. No presente estudo, investigou-se a participação de C. diphtheriae e das proteínas de superfície 67-72p na aderência à Fn e ao Fbn de plasma humano e a eritrócitos. A aderência às células HEp-2 e internalização também foram analisadas. A participação de 67-72p nos mecanismos de morte celular foi avaliada através das colorações por Azul de Tripan e 46-diamidino-2-fenil indol (DAPI), pelo ensaio de redução utilizando dimetil-tiazol-difenil tetrazólio (MTT) e por citometria de fluxo. As 67-72p foram extraídas da superfície da amostra toxigênica C. diphtheriae subsp. mitis CDC-E8392 através de processos mecânicos e precipitação com sulfato de amônio saturado. Análises por SDS-PAGE e immunoblotting detectaram a presença das bandas protéicas de 67 e 72kDa nas amostras toxinogênicas e atoxinogênicas analisadas, as quais pertenciam aos biotipos fermentador e não fermentador de sacarose. C. diphtheriae foi capazes não só de formar agregados na presença de plasma de coelho, mas também de converter Fbn em fibrina independentemente da presença do gene tox. No entanto, a amostra atoxinogênica ATCC 27010 (tox-) foi menos aderente ao Fbn do que a homóloga ATCC 27012 (tox+). A interação bacteriana com eritrócitos foi inibida somente pela Fn. Ligações entre Fn e/ou Fbn com 67-72p foram demonstradas por dot blotting, ELISA e/ou ensaios utilizando fluorescência. As 67-72p foram capazes de inibir as interações bacterianas com o Fbn, indicando que 67-72p podem participar do processo de aderência do patógeno aos tecidos do hospedeiro. Através da microscopia óptica, demonstrou-se a ligação de 67-72p adsorvidas em microesferas de látex com células HEp-2. Anticorpos de coelho do tipo IgG anti 67-72p interferiram somente com a expressão do padrão de aderência do tipo difuso, normalmente apresentado pela amostra CDC-E8392. A Microscopia Eletrônica de Transmissão (MET) e a inibição da internalização bacteriana pela IgG anti 67-72p ou por 67-72p indicaram o papel de 67-72p como invasina. Alterações do citoesqueleto de células HEp-2 com acumulação de actina polimerizada, induzida por microesferas sensibilizadas com 67-72p, foi observada pelo fluorescent actin staining (FAS) test. Foi visualizado um aumento no número de bactérias viáveis no compartimento intracelular após tratamento de células HEp-2 ou dos microrganismos com Fn. A presença de partículas de látex adsorvidas com 67-72p no interior de vacúolos frouxos em células HEp-2 sugeriu que estas proteínas podem causar efeito citotóxico. A avaliação através das colorações com Azul de Tripan, DAPI e os ensaios de redução utilizando MTT demonstraram um decréscimo na viabilidade de células tratadas com 67-72p. As mudanças morfológicas observadas 3 horas após o início do tratamento com 67-72p incluíram vacuolização, fragmentação nuclear e formação de corpúsculos apoptóticos. A citometria de fluxo revelou um decréscimo de 15,13% no volume/tamanho de células tratadas com 67-72p. Além disso, o ensaio utilizando Iodeto de Propídio (IP) e Anexina V (AV)-FITIC demonstrou que havia 66,1% de células vivas (IP-/AV-), 16,6% de células em apoptose inicial (IP-/AV+) e 13,8% de células em apoptose tardia ou necrose secundária. Em conclusão, as 67-72p estão diretamente envolvidas na interação com Fn e Fbn. As proteínas não fimbriais 67-72p são hemaglutininas implicadas na aderência a células respiratórias e na internalização. Além disso, estas proteínas podem atuar como fatores de virulência em potencial para induzir apoptose de células epiteliais nos estágios iniciais da difteria e nas infecções invasivas causadas pelo C. diphtheriae
Corynebacterium diphtheriae have been isolated from classical diphtheria and systemic infections such as endocarditis. Fibrinogen (Fbn) and fibronectin (Fn) are high molecular-weight glycoproteins that may be found in extracellular matrix of connective tissues. Their influence in the pathogenesis of local and in invasive C. diphtheriae infection is object of interest due to the fact that diphtheria bacilli is recovered from lesions where such proteins are predominant, including pharyngeal pseudomembrane and valve heart vegetations in infectious endocarditis. There is growing evidence that C. diphtheriae may adhere to and be internalized by cells in culture. The present study investigated the participation of C. diphtheriae strains and 67-72p, a surface protein, in adherence to human plasma Fn, Fbn, erythrocytes, adherence to and internalization by HEp-2 cells. The participation of 67-72p in promoting cell death was evaluated by the Trypan blue, DAPI staining methods, methylthiazole tetrazolium (MTT) reduction assay and flow cytometry. The 67-72p was extracted from C. diphtheriae subsp. mitis CDC-E8392 toxigenic strain, by mechanical process and ammonium sulfate fractionation. SDS-PAGE and immunoblotting analysis detected the polypeptide bands of 67 and 72 kDa in all toxigenic and nontoxigenic strains from both sucrose-fermenting and non-fermenting biotypes. Diphtheria bacilli were capable to both form bacterial aggregates in rabbit plasma and to convert Fbn to fibrin independently to the presence of tox gene, albeit the ATCC 27010 (tox-) strain was less adherent to Fbn than the parental strain ATCC 27012 (tox+). Bacteria-erythrocytes interaction was inhibited only by Fn. Interactions of Fn and/or Fbn with 67-72p were demonstrated by dot blotting, ELISA and/or fluorescence assays. Bacteria-Fbn interaction was inhibited by 67-72p, indicating that 67-72p may participate in the adhesion of the pathogen to host tissues. The interaction of HEp-2 cells with 67-72p-adsorbed latex microspheres was demonstrated by light microscopy. Rabbit IgG anti 67-72p was shown to interfere with diffuse adherence phenotype to HEp-2 cells displayed by CDC-E8392, but not by other phenotypes. Transmission electron microscopy (TEM) and the inhibition of bacterial internalization by anti 67-72p IgG and 67-72p indicated the role of 67-72p as invasin. Cytoskeletal accumulation of polymerized actin in HEp-2 cells induced by 67-72p-microspheres was observed by the fluorescent actin staining (FAS) test. Fn enhanced the intracellular viability of all strains tested. The presence of 67-72p-latex particles inside spacious vacuoles (SV) in HEp-2 cells, suggested a citotoxic effect of these proteins. Evaluation by the Trypan blue staining method, 4,6-Diamidine-2-phenylindole dihydrochloride DAPI and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay showed a significant decrease in viability of HEp-2 cells treated with 0.2 mg/ml 67-72p. Morphological changes in HEp-2 cells (vacuolization, nuclear fragmentation, and the formation of apoptotic bodies) was observed after 3 h post-treatment with 67-72p. Flow cytometry revealed a 15.13% reduction apoptotic volume of HEp-2 cells treated with 0.2 mg/ml 67-72p. Moreover, a double-staining assay using Propidium Iodide (PI)/Annexin V (AV) demonstrated the numbers of vital (PI-/AV-) (66.1%) vs. early apoptotic (PI-/AV+) (16.6%) cells and late apoptotic or secondary necrotic cells (PI+/AV+) (13.8%). In conclusion, the 67-72p are directly implicated in C. diphtheriae interaction with Fn and Fbn. The non-fimbrial Fn/Fbn binding 67-72p are hemagglutinins directly implicated in adherence to and internalization by respiratory epithelial cells. Moreover, 67-72p may act as a potential virulence factor to induce apoptosis of epithelial cells in the early stages of diphtheria and C. diphtheriae invasive infection
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O'Brien, Dawne, Ashley Santa-Cruz i Amy Kennedy. "Assessing Adherence to the Tetanus, Diphtheria and Pertussis Vaccination Guidelines at a Federally Qualified Health Center Before and After a Clinical Pharmacist Intervention". The University of Arizona, 2014. http://hdl.handle.net/10150/614235.
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Class of 2014 AbstractSpecific Aims: Tetanus, diphtheria, and pertussis are diseases, which are preventable through proper vaccination. In spite of the availability these vaccines, however, there has recently been a surge in the number of pertussis cases in the United States. The objective of this study is to determine provider adherence to tetanus, diphtheria and pertussis guidelines set forth by the Advisory Committee on Immunization Practices in a primary care setting before and after a clinical pharmacist intervention. Methods: A retrospective cohort of chart reviews was conducted between January 1 – September 30, 2013 to determine immunization adherence to tetanus, diphteria, and pertussis vaccination guidelines. A clinical pharmacist then preformed a series of cross-sectional chart reviews as an intervention. Following the intervention, a retrospective chart review was conducted to evaluate if Tdap vaccination rates improved between March 17-23, 2014. Main Results: Overall immunization rates greatly improved following the intervention (p<0.0001; x2=44.988). For non-pregnant adults between the ages of 19-64 the vaccination rate improved from 26% to 61.1% (p<0.0001; x2=47.07). A statistically significant improvement was not seen in the groups with patients 65 or older or pregnant women (p>0.05). Tdap vaccination status was appropriately evaluated and vaccinations given by primary doctors improved from 17.7% to 61.2% and those prescribed by nurse practitioners improved from 22.4% to 56.3%. Conclusion: Intervention by a Clinical Pharmacist helped improve overall provider adherence to the tetanus, diphteria, and pertussis vaccination guidelines.
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Flores-Canales, Jose C. "Computational Studies of Acidic Destabilization and Membrane Association of Diphtheria Toxin Translocation (T) Domain". Research Showcase @ CMU, 2014. http://repository.cmu.edu/dissertations/1038.
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Diphtheria toxin translocation (T) domain is a water soluble protein that consists of ten alpha-helices in high pH solution. Experimental studies have determined that T-domain undergoes conformational changes upon decrease of solution pH, which shifts the protein population from its initial water soluble to a membrane-competent in solution. It was hypothesized that conformational changes of the latter state prepare the protein structure for subsequent membrane binding. After binding, refolding of T-domain on the membrane results in the formation of a transmembrane state, which is characterized by the permeation of the lipid bilayer. The function of transmembrane state is to help the translocation of a catalytic domain attached to the protein N-terminal across the lipid bilayer. The first goal of this work is to study the pH-dependent destabilization of T-domain structure in solution and understand the role of protonation of key residues using a variety of computational and experimental methods. The second goal is to study the subsequent membrane binding of T-domain to lipid bilayers and propose a theoretical model of the early steps of T-domain refolding on the membrane interface using a multiscale approach. Modeling of the low pH induced conformational changes and membrane association of T-domain is performed in two stages. In the first stage, protonation of N-terminal histidines triggers conformational changes of the N-terminal helices of T-domain in solution. The role of histidines was confirmed by thermodynamic integration, continuum electrostatic calculations, and microsecond long molecular dynamics (MD) simulations. Two microsecond MD simulations of a low pH model of T-domain sampled similar destabilized protein conformations; however, an N-terminal helix showed dissimilar degree of refolding. To improve the sampling of conformational changes, we proposed and implement a sampling method based on the accelerated molecular dynamics simulations method. Our proposed implementation accelerates the sampling of the conformational landscape of the low pH T-domain model by boosting the direct-space electrostatic interactions of solute-solute atom pairs. In general, this implementation accelerates the sampling of the conformational space of alanine-dipeptide in comparison to the original implementation of accelerated molecular dynamics. In the second stage, a multiscale approach is used to model the membrane association of the low pH destabilized model of T-domain to lipid bilayers of different compositions. Two preferable membrane-bound conformations of the low pH T-domain model are predicted by equilibrium and free energy calculations. The most frequently observed membrane-bound conformation is stabilized by electrostatic interactions between the protein and the lipid headgroups. In contrast, the less frequently observed membrane-bound conformation is stabilized by hydrophobic interactions between the protein and lipid headgroups. These interactions allow for a deeper insertion of T-domain in the membrane interface. The predicted membrane-bound conformations were refined by atomistic molecular dynamics simulations, which show that membrane-bound conformations are stable for several microseconds. Furthermore, atomistic MD simulations suggested that neutralization of glutamate and aspartate sidechains favored a deeper inserted state of T-domain in the membrane interface. This observation is in good agreement with reported pH-dependent insertion of T-domain in the membrane interface. To study the assembly of transmembrane helices, a coarse-grained model based on a residue level of representation and a rigid-body Monte-Carlo sampling method is developed. The scoring energy function is constructed using a knowledge based potential extracted from water soluble protein structures. To compensate the protein interior packing and the solvation differences, an experimentally determined membrane partition scale for all residues was used. This scoring function was tested in a set of three transmembrane homodimers. The proposed scoring function and the associated rigid-body Monte-Carlo sampling method can be applied in the first steps of prediction of near-native structures of transmembrane proteins followed by structural refinement using atomistic MD simulations.
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Persson, Johan. "De som aldrig återvände : Hur Kroppa landskommun drabbades av spanska sjukan". Thesis, Karlstads universitet, Institutionen för samhälls- och kulturvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-34936.
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Wermland was affected by the Spanish flu like the Swedish national average, about a half percentage of Wermlands population would lose their lives to the flu during the autumn 1918. The flu has for many fallen into oblivion. This oblivion is so wide spread that it´s possible to talk about a "collective forgetfulness". The society have selected to remember 1918 for "when the guns went quiet on the western front" and not for the millions who died from the treacherous Spanish flu. The world had already suffered enough from the four years of war that had been fought, thus the victims of the flu would be honored but would soon fade in to oblivion. When you investigate deeper you get the picture that the national average don´t do Wermland and its cities or rural areas any justice when a large variations seems to occur within regional areas. One of Sweden's hardest effected cities was Kristinehamn and some miles north of this city you could find Kroppa rural county. This small county focused on iron works has two small central communities. Both of them had iron/tube mill owned by the same company, Storfors Bruk AB. During the autumn of 1918, Kroppa came in firsthand experience the Spanish flu and it´s expansion, which will get considerable effects how people in these areas could live their lives. As this wouldn´t be enough a diphtheria epidemic would also cause havoc and despair in Kroppa at the same time as the flu. The diphtheria will harvest new victims from a group that during the flu had been relative safe, the children. Even that Kroppa rural county experience a difficult period there behavior will prevent that fear are spread to the public.
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Антушева, Т. І. "Бактеріологічний моніторинг поширеності збудників дифтерії". Thesis, Сумський державний університет, 2016. http://essuir.sumdu.edu.ua/handle/123456789/45300.
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У сучасному світі реалізація епідемічного процесу інфекцій, що керуються засобами вакцинопрофілактики (керовані інфекції), відбувається у вигляді безсимптомного бактеріоносійства. Проблема зазначеного явища полягає у тому, що інтенсивна циркуляція збудників серед різних верств населення є неконтрольованим стихійним процесом. На сучасному етапі епідемічного благополуччя стратегія боротьби з зазначеними інфекціями, зокрема дифтерійною інфекцією, спрямована на профілактику персистенції збудників та зниження рівня бактеріоносійства. Таким чином, епідеміологічний контроль повинен ґрунтуватись не тільки на даних щодо рівня захворюваності та носійства у осередках захворювань, але й враховувати динаміку циркуляції цих збудників серед здорового населення. Саме тому наразі набуває надзвичайної актуальності впровадження цілеспрямованих моніторингових досліджень на носійство збудників дифтерії серед найбільш уражених верств населення, зокрема дітей, яке спостерігається на тлі вакцинопрофілактики.
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Wolff, Christian. "Characterization of the translocation mechanism of the Diphtheria toxin catalytic domain across a lipid membrane". Doctoral thesis, Universite Libre de Bruxelles, 2001. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211678.
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Gingrich, Penny. "Susceptibility to tetanus and diphtheria in recently arrived adult immigrants and refugees to Montreal, Quebec". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86891.
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Background: Adult immigrants may have been under-immunized in their countries of origin. We estimated the seroprevalence and examined risk factors for susceptibility to diphtheria and tetanus.Methods: 1480 newly-arrived adult immigrants were recruited in Montreal, 2002-2004. We collected socio-demographic information and vaccination history, and measured serum antibodies to tetanus and diphtheria by EIA to identify susceptibility, defined as ≤0.15 IU/ml and ≤0.10 IU/ml, respectively.
Results: 45% (95% CI, 42%-48%) of immigrants, mean age 31 +/- 8.6 years, lacked immunity to either tetanus or diphtheria, ranging by region of origin (23%-79%). 32% (95% CI, 30%-34%) were susceptible to tetanus and susceptibility increased with age. Susceptibility to diphtheria was less prevalent [26% (95% CI, 24%-28%)] and decreased with age.
Conclusions: Many adult immigrants would benefit from diphtheria/tetanus vaccine. Susceptibility to tetanus suggests under-vaccination, while decreasing susceptibility to diphtheria with age suggests that immunity has been boosted from ongoing transmission in some countries of origin.
Introduction: Les immigrants adultes sont peut-être sous-immunisés dans leurs pays d'origine. Nous avons effectué une étude de la prévalence de la susceptibilité au tétanos et à la diphtérie et nous avons examiné les indicateurs potentiels de cette susceptibilité.
Méthodes: 1480 adultes ayant immigré récemment ont été recrutés à Montréal entre 2002 et 2004. Nous avons obtenus des informations sociodémographiques et l'histoire de vaccination et nous avons mesuré les anticorps sériques contre le tétanos et la diphtérie avec le test EIA; la susceptibilité était définie comme ≤0.15 IU/ml et ≤0.10 IU/ml, respectivement.
Résultats: Quarante-cinq pour cent (95% IC, 42%-48%) des immigrants, avec un âge moyen de 31 +/- 8.6 ans, n'étaient pas immuns soit contre le tétanos ou la diphtérie, avec des variations selon la région d'origine (23%-79%). Trente-deux pour cent (95% IC, 30%-34%) étaient susceptibles au tétanos et la susceptibilité augmentait avec l'âge. La susceptibilité à la diphtérie était moins prévalente [26% (95% IC, 24%-28%)] et diminuait avec l'âge.
Conclusions: Plusieurs immigrants adultes bénéficieraient du vaccin contre le tétanos et la diphtérie. La susceptibilité au tétanos suggère la présence de sous-vaccination, tandis que la susceptibilité à la diphtérie, qui diminue avec l'âge, suggère que l'immunité a été stimulée par la transmission continue de l'infection dans certains pays d'origine.
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Cheung, Wing-Tai. "Application of diphtheria toxin and an anti-receptor antibody in studies of cellular signal transduction". Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386348.
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Hautaniemi, V. (Vesa). "Towards the discovery of chemical probes for diphtheria toxin-like human adenosine diphosphate ribosyltransferase 3". Master's thesis, University of Oulu, 2015. http://urn.fi/URN:NBN:fi:oulu-201512012189.
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Diphtheria toxin-like human ADP-ribosyltransferase 3 (ARTD3) is a poorly characterized member of the ARTD superfamily of enzymes. ARTDs are enzymes that catalyze ADP-ribosylation, a reversible post-translational modification whereby growing chains of ADP-ribose is attached onto target proteins. ARTDs are involved in a wide variety of roles within the cell, including DNA damage repair and maintenance of genomic stability. ARTD3 is activated by damaged DNA and believed to play a role in double-strand break repair (DSBR) in the non-homologous end-joining (NHEJ) pathway, and has been implicated as a drug target in the treatment of cancer. In this study, an activity assay previously reported for other ARTDs was adopted for ARTD3 in order to screen the enzyme with two compound libraries consisting of 918 compounds in order to discover new potential chemical probes for the protein. The assay was validated through statistical criteria and its performance tested in a preliminary screen with 32 known ARTD inhibitors and their analogs. From all the compounds screened, 12 were ordered and 8 verified as hits in a counter-screen at 10 µM compound concentration. These 8 compounds were then further characterized with thermofluor to determine their ability to bind ARTD3 catalytic domain, fluorescence polarization (FP) to determine their effects on ARTD3’s binding affinity with DNA and the compounds had their IC50 values were measured. 6 compounds that exhibited interesting results in these experiments were classified according to their proposed mechanism of inhibition or compound class. These compounds consisted of two DNA chelating topoisomerase inhibitors, one insecticide, one heavy-metal containing polycyclic hydrocarbon (PHC) and two unclassified tumor suppressors. None of the compounds stabilized full-length ARTD3 or the catalytic fragment, but the DNA chelating agents lowered the binding affinity of ARTD3 to DNA. While no traditional ARTD inhibitor with potential for use as a chemical probe was discovered, the effects of DNA chelating agents on ARTD3’s binding affinity with DNA could be further investigated via binding affinity studies such as isothermal titration calorimetry (ITC). One of the unclassified tumor suppressors with decent potency (IC50: 2.7 µM) could also be tested against other ARTDs and if it was found to be selective against ARTD3, its binding to ARTD3 could be determined with co-crystallization and x-ray crystallography.
35
Watermeyer, Katy. "Public health in Cape Town 1923-1944: diphtheria, dairies and the discovery of the child". Master's thesis, Faculty of Humanities, 2000. http://hdl.handle.net/11427/30827.
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Puumalainen, Taneli. "An eleven valent diphtheria and tetanus-conjugated pneumococcal vaccine immunogenicity and safety in Filipino infants". Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/puumalainen/.
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Rydell, Niclas. "Development of a New Oral Vaccine against Diphtheria and the Study of its Immunogenicity in Mouse and Man". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4629.
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Pallen, Mark John. "Detection and characterisation of diphtheria toxin genes and insertion sequences by PCR and other molecular techniques". Thesis, Queen Mary, University of London, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245105.
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Johnson, Nicholas. "Construction of a novel epitope expression vector based on the B-subunit of the diphtheria toxin". Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296057.
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Mezones-Holguin, Edward, Ali Al-kassab-Córdova, Jorge L. Maguiña i Alfonso J. Rodriguez-Morales. "Vaccination coverage and preventable diseases in Peru: Reflections on the first diphtheria case in two decades during the midst of COVID-19 pandemic". Elsevier Inc, 2021. http://hdl.handle.net/10757/655819.
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Васильєв, Юрій Костянтинович, Юрий Константинович Васильев, Yurii Kostiantynovych Vasyliev, Микола Дмитрович Чемич, Николай Дмитриевич Чемич, Mykola Dmytrovych Chemych, Оксана Миколаївна Чемич, Оксана Николаевна Чемич i Oksana Mykolaivna Chemych. "Особливості епідемії дифтерії в умовах північно-східного регіону України". Thesis, Вид-во СумДУ, 2010. http://essuir.sumdu.edu.ua/handle/123456789/3745.
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Мета роботи - вивчення клініко-епідеміологічних особливостей сучасної
дифтерії в умовах північно-східного, прикордонного регіону України.
Об’єкт дослідження - медичні карти хворих на дифтерію з 1987 по
2005 рр. Епідеміологічні карти хворих за цей же період.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/3745
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Красовицький, Зіновій Йосипович, Зиновий Иосифович Красовицкий, Zinovii Yosypovych Krasovytskyi, Ірина Олександрівна Троцька, Ирина Александровна Троцкая, Iryna Oleksandrivna Trotska, Е. П. Панченко i В. А. Бороденко. "Применение гипохлорита натрия в комплексном лечении больных дифтерией, злоупотребляющих спирными напитками". Thesis, Издательство СумГУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24736.
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Красовицький, Зіновій Йосипович, Зиновий Иосифович Красовицкий, Zinovii Yosypovych Krasovytskyi, Ірина Олександрівна Троцька, Ирина Александровна Троцкая, Iryna Oleksandrivna Trotska, Лариса Петрівна Кулеш, Лариса Петровна Кулеш, Larysa Petrivna Kulesh i Л. М. Лазарева. "Влияние хронической алкогольной интоксикации на течение дифтерии". Thesis, Издательство СумГУ, 1997. http://essuir.sumdu.edu.ua/handle/123456789/24742.
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Truter, Erika Mare. "Chitosan derived formulations and EmzaloidTM technology for mucosal vaccination against diphtheria : nasal efficacy in mice / Erika M. Truter". Thesis, North-West University, 2005. http://hdl.handle.net/10394/858.
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Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan
chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery
of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily
form microparticles and nanoparticles, which have the ability to encapsulate large
amounts of antigens. Emzaloid™ technology has proven in the past to be an effective
delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large
amounts of drugs including vaccines.
In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles
as well as micrometer and nanometer range Emzaloids to enhance both the systemic and
mucosal (local) immune response against diphtheria toxoid (DT) after nasal
administration in mice was investigated.
The above mentioned formulations were prepared and characterised according to size and
morphology. DT was then associated to the chitosan microparticles and nanoparticles as
well as TMC microparticles to determine the antigen loading and release. It was found
that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 %
respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and
18.3 %.
DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC
microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate
buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated
subcutaneous with DT associated to alum as a positive control. All mice were vaccinated
on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti-
DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked
imrnunosorbent assay (ELISA).
In the study conducted to determine the systemic (IgG) and local (IgA) immune
responses it was seen that DT associated to all the experimental formulations produced a
systemic immune response. The said formulations produced a significantly higher
systemic immune response when compared to the formulation of DT in PBS.
Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a
much higher systemic immune response than the mice that were vaccinated
subcutaneously with DT associated to alum, whereas the other formulations produced
systemic immune responses that were comparable to that of DT associated to alum. It was
also found that DT associated to the experimental formulations produced a local immune
response, however only DT associated to TMC microparticles produced a consistent local
immune response.
It can be concluded from the in vivo experiments that the TMC formulations, moreover,
the TMC microparticles is the most effective and promising formulation for the nasal
delivery of vaccines.Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
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Van, der Westhuizen Elaine. "Chitosan derived formulations and EmzaloidTM technology for mucosal vaccination against diphtheria : oral efficacy in mice / Elaine van der Westhuizen". Thesis, North-West University, 2004. http://hdl.handle.net/10394/633.
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Vaccination plays a very important part in daily life. It is essential to get vaccinated at an
early age. The conventional parented method used is not always effective and not cost
efficient. It requires qualified personnel and sterile conditions for administration of the
vaccines.
The aim of this study was to investigate the effect of chitosan, N-trimethyl chitosan
chloride (TMC) and Emzaloid™ particles on the local and systemic immune response of
mice after oral vaccination with Diphtheria toxoid (DT). The different formulations used
were chitosan microparticles (± 10 µm), chitosan nanoparticles (± 400 nm), TMC
microparticles (± 5 µm), Emzaloid microparticles (± 4 µm) and Emzaloid nanoparticles
(± 500 nm). All of these formulations proved to be very good delivery systems and can
entrap large amounts of the antigen.
Balb/c mice were used to determine the local and systemic immune response of these
formulations. The mice were vaccinated orally on three consecutive days in week 1 and
3 with 40 Lf DT per week with a total volume of 300 µl. Blood samples were taken from
the mice and analysed for a systemic immune response (IgG). The same mice were used
to determine the local immune response (IgA). Faeces were collected from each mouse
on day 1, 3, 4, 6, 14 and 20 for analysis. An enzyme-linked immunosorbent assay
(ELISA) was used to determine IgG and IgA titers.
It can be concluded that chitosan nanoparticles was the only formulation with a higher
response than that of the currently used vaccine. Emzaloid nanoparticles showed no
significant difference in response when compared to the currently used vaccine. All the
other formulations showed a much smaller response than that of the conventional method
of vaccination.Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
46
Helmy, Hannah Louise. "“This Isn’t Like Diphtheria, You Know?”: The Sociocultural Context of Human Papillomavirus Immunization, Potential Mandates, and Narratives of Risk Among". Scholar Commons, 2008. https://scholarcommons.usf.edu/etd/288.
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Many in the biomedical community have praised the recently released Human Papillomavirus (HPV) vaccine, Gardasil, for having the potential to significantly reduce the disease burden of cervical cancer and genital warts. However, complex intersections of ideology, morality, and politics have made this new vaccine considerably contested, particularly as public debate has turned to the ethics of state-mandated HPV vaccination for 11-12 year old girls. Subsequently, the extent to which mandatory vaccinations are accepted by parents and implications regarding the infringement of these coercive measures on their rights to make health care decisions for their children has become powerfully positioned in public discourse. This research seeks to examine how mothers of girls conceptualize Gardasil and the potential mandates in order to illuminate the multi-faceted socio-cultural context of risk embedded within this immunization. Major themes that emerged from in-depth interviews include diverse perceptions of the risk of HPV for their daughter(s) specifically, children as actual or potential sexual beings, concerns about vaccine safety, mistrust of pharmaceutical companies and government collusion, and conceiving of vaccination against HPV as imbued with a either a moral or cancer prevention subtext. The need for collaboration and communication between the medical and governmental institutions who promote vaccines such as Gardasil and the public who politically and socially consumes them has been apparent throughout my research. Applied anthropologists have a unique role to play by situating diverse stakeholder perspectives across interdisciplinary fields in order to develop more appropriate and informed policies.
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Helmy, Hannah Louise. ""This isn't like diphtheria, you know? : the sociocultural context of Human Papillomavirus immunization, potential mandates, and narratives of risk among mothers". [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002712.
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Чемич, Микола Дмитрович, Николай Дмитриевич Чемич, Mykola Dmytrovych Chemych, Юрій Костянтинович Васильєв, Юрий Константинович Васильев i Yurii Kostiantynovych Vasyliev. "Клинико-эпидемиологические особенности дифтерии на современном этапе". Thesis, Изд-во СумГУ, 2007. http://essuir.sumdu.edu.ua/handle/123456789/5017.
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На рубеже тысячелетий дифтерия остается проблемой современной медицины. Тому подтверждение - подъем заболеваемости дифтерией, который наблюдался в Украине на исходе второго тысячелетия.
Цель исследования – изучение клинико-эпидемиологических особенностей течения дифтерии в современных условиях.
При цитировании документа, используйте ссылку http://essuir.sumdu.edu.ua/handle/123456789/5017
49
Pereira, Martha Maria Mutti. "Eficácia da associação da vacina tríplice ao BCG". Universidade de São Paulo, 1986. http://www.teses.usp.br/teses/disponiveis/6/6135/tde-20122017-111313/.
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A eficácia da associação quádrupla (DPT + BCG) foi estudada através da proteção e comparação da soro conversão das vacinas, usando como adjuvante o hidróxido de alumínio e ou BCG. A potência da vacina pertussis foi avaliada pelo teste de proteção em camundongos e o BCG pelo teste de consumo de oxigênio e de vitalidade, sendo considerada satisfatória. Sendo os toxóides diftérico e tetânico considerados proteínas inertes e estáveis, suas potências não foram determinadas depois de associadas. Os níveis de anticorpos foram determinados para difteria e tétano pela reação imunoenzimática, para vacina pertussis pela reação de imunofluorescência e para o BCG pela conversão tuberculínica. Os níveis de conversão foram satisfatórios, revelando ser possível a associação sem prejuízo para nenhum dos antígenos. A associação DPT + BCG não causou reação local ou geral significante, possibilitando uma simplificação operacional.The efficacy of the quadruple association (DPT + BCG) was studied though protection and comparison ot the conversion serum in vaccines using aluminium hydroxide or BCG as adjuvant. Both the protection power of the Pertussis vaccine evaluated by the protection test in mice and BCG by the oxygen uptake and counts of viable particles were considered satisfactory. Being difteria and tetanus toxoids considered inert and stable proteins, their protection wasn\'t determined after their combination. The antibody levels produced by the antigens were determined by the enzyme-linked immunosorbent assay to the difteria and tetanus toxoids, by the fluorescent antibody technique to the Pertussis vaccine and by the tuberculin conversion to the BCG. The conversion levels were satisfatory and there was no damage in their association. There was no meaningful local or general reaction in this association making an operational simplification possible.
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Бинда, Тетяна Парфеніївна, Татьяна Парфеньевна Бында, Tetiana Parfeniivna Bynda, В. А. Рашевська i В. В. Тіщенко. "Результати серологічного скринінгу стану колективного імунітету населення Сумської області до збудників кору та дифтерії". Thesis, Видавництво СумДУ, 2010. http://essuir.sumdu.edu.ua/handle/123456789/6216.
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