Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar

Detalhes bibliográficos
Autor(a) principal: Almeida Júnior, Pedro Sousa de
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
Texto Completo: http://repositorio.ufes.br/handle/10/14404
Resumo: Tuberculosis (TB) is one of the oldest infectious-contagious diseases in the world and the eradication of which remains a challenge. One of the major problems related to TB is the latent infection in which Mycobacterium tuberculosis (MTB) is found in its host in a metabolic state characterized as "numbness". In this state, the microorganism is not recognized by the immune system and is not detected by conventional diagnostic methods. This work aims to detect metabolically diverse populations of MTB in sputum samples of patients with pulmonary TB and to analyse the influence of tuberculosis therapy on these bacilli. The secondary objective of this study is to verify whether persistent bacilli populations may imply therapeutic failure. For this purpose, the 48 wells plate dilution technique was used, which determines the amount of microorganisms by calculating the Most Probable Number (MPN). The MPN determines the amount of microorganisms that grow in liquid medium (7H 9) and in liquid medium after the addition of liquid culture supernatant of MTB (SN). In addition, conventional diagnostic methods, bacilloscopy and solid and liquid cultures were performed. Sputum samples were collected prior to treatment (M0) and monthly until the end of treatment (M1 to M6). To lower the rate of contamination during the procedure, oral hygiene with chlorhexidine 0.12% was standardized. The preliminary clinical and epidemiological data show that the population studied is young (39.6 ± 19.4), with body mass index (BMI) within the international standards of normality (20.5 ± 1.6), being 57% male patients and 43% female. The most reported symptoms were cough and fever, with time of disease progression around 1 to 3 months as the most frequent period (71% for each). The preliminary radiographic data indicate that all patients had radiographic images suggestive of abnormal TB, with six (86%) of these patients characterized with advanced disease and one (14%) with moderate, with the same proportion found in relation to cavitation. The microbiological data reveal that only one (20%) of the conventional cultures (Ogawa or MGIT) remained positive for MTB after two months of treatment. A preliminary analysis indicated that 84% of the bacilli of the samples M0 and 98% of the M1-M4 samples are dormant or SN-dependent bacilli. When analysing the effect of TB therapy on the different MTB populations in sputum samples of patients under treatment, a progressive decrease in the amount of microorganisms over the months of treatment was observed, mainly in relation to metabolically active microorganisms.
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spelling Palaci, Moiseshttps://orcid.org/0000000320136071http://lattes.cnpq.br/2602694352713051Almeida Júnior, Pedro Sousa dehttps://orcid.org/http://lattes.cnpq.br/9774221817421517Spano, Liliana Cruzhttps://orcid.org/0000000262056988http://lattes.cnpq.br/7451382455806895Santos, Kenia Valeria doshttps://orcid.org/http://lattes.cnpq.br/9074173162086323Ribeiro, Fabiola Karla Correahttps://orcid.org/http://lattes.cnpq.br/9887373751252283Hadad, David Jamilhttp://lattes.cnpq.br/17800851425051902024-05-30T00:49:08Z2024-05-30T00:49:08Z2019-08-16Tuberculosis (TB) is one of the oldest infectious-contagious diseases in the world and the eradication of which remains a challenge. One of the major problems related to TB is the latent infection in which Mycobacterium tuberculosis (MTB) is found in its host in a metabolic state characterized as "numbness". In this state, the microorganism is not recognized by the immune system and is not detected by conventional diagnostic methods. This work aims to detect metabolically diverse populations of MTB in sputum samples of patients with pulmonary TB and to analyse the influence of tuberculosis therapy on these bacilli. The secondary objective of this study is to verify whether persistent bacilli populations may imply therapeutic failure. For this purpose, the 48 wells plate dilution technique was used, which determines the amount of microorganisms by calculating the Most Probable Number (MPN). The MPN determines the amount of microorganisms that grow in liquid medium (7H 9) and in liquid medium after the addition of liquid culture supernatant of MTB (SN). In addition, conventional diagnostic methods, bacilloscopy and solid and liquid cultures were performed. Sputum samples were collected prior to treatment (M0) and monthly until the end of treatment (M1 to M6). To lower the rate of contamination during the procedure, oral hygiene with chlorhexidine 0.12% was standardized. The preliminary clinical and epidemiological data show that the population studied is young (39.6 ± 19.4), with body mass index (BMI) within the international standards of normality (20.5 ± 1.6), being 57% male patients and 43% female. The most reported symptoms were cough and fever, with time of disease progression around 1 to 3 months as the most frequent period (71% for each). The preliminary radiographic data indicate that all patients had radiographic images suggestive of abnormal TB, with six (86%) of these patients characterized with advanced disease and one (14%) with moderate, with the same proportion found in relation to cavitation. The microbiological data reveal that only one (20%) of the conventional cultures (Ogawa or MGIT) remained positive for MTB after two months of treatment. A preliminary analysis indicated that 84% of the bacilli of the samples M0 and 98% of the M1-M4 samples are dormant or SN-dependent bacilli. When analysing the effect of TB therapy on the different MTB populations in sputum samples of patients under treatment, a progressive decrease in the amount of microorganisms over the months of treatment was observed, mainly in relation to metabolically active microorganisms.A tuberculose (TB) é uma das doenças infectocontagiosas mais antigas do mundo cuja erradicação continua sendo uma desafio. Um dos maiores problemas relacionados à TB é a infecção latente em que o Mycobacterium tuberculosis (MTB) é encontrado em seu hospedeiro em um estado metabólico caracterizado como “dormência”. Neste estado, o microrganismo não é reconhecido pelo sistema imunológico e não é detectado pelos métodos convencionais de diagnóstico. Esse trabalho tem como objetivo detectar populações metabolicamente diversas de MTB em amostras de escarro de pacientes com TB pulmonar e analisar a influência da terapia antituberculose sobre estes bacilos. O objetivo secundário do estudo é verificar se populações de bacilos persistentes podem implicar em insucesso terapêutico. Para tanto, foi utilizada a técnica de diluição em placa de 48 poços, a qual calcula a quantidade de microrganismos por meio do cálculo de Número Mais Provável (NMP). O determina a quantidade de microrganismos que crescem em meio líquido (7H9) e em meio líquido após adição de filtrado de cultura líquida de MTB (FC). Adicionalmente, foram realizados métodos convencionais de diagnóstico, baciloscopia e culturas sólida e líquida. Amostras de escarro foram coletadas antes do início de tratamento (M0) e mensalmente até o final do tratamento (M1 a M6). Para assegurar uma diminuição na taxa de contaminação durante o procedimento, a utilização de higienizante oral (clorexidina 0,12%) foi padronizada. Os dados clínicos e epidemiológicos evidenciam que a população estudada é jovem (39,6 ± 19,4), com Índice de Massa Corporal (IMC) dentro dos padrões internacionais de normalidade (20,5 ± 1,6), sendo 57% dos pacientes do sexo masculino e 43% do sexo feminino. Os sintomas mais frequentes foram tosse e febre, com tempo de evolução da doença em torno de 1 a 3 meses como período mais frequente (71% para cada). Os dados radiográficos demonstram que todos os pacientes possuíam imagens radiográficas sugestivas de TB, de caráter anormal, sendo que seis (86%) destes pacientes foram caracterizados com doença avançada e um (14%) com moderada, com mesma proporção encontrada em relação à cavitação. Os dados microbiológicos mostram que somente uma (20%) das culturas convencionais (Ogawa ou MGIT) permaneceu positiva para MTB após dois meses de tratamento. A análise dos dados indicou que 84% dos bacilos das amostras M0 e 98% das amostras M1-M4 são bacilos dormentes ou dependentes de FC. Ao analisar o efeito da terapia anti-TB sobre as diferentes populações de MTB nas amostras de escarro de pacientes em tratamento, foi observada uma diminuição progressiva na quantidade de microrganismos ao longo dos meses de tratamento, principalmente em relação aos microrganismos metabolicamente ativos. Dessa forma conclui-se que o uso de FC é uma ferramenta importante para a redução do tempo de positivação das culturas e que MTB na sua forma metabólica dormente é mais tolerante às drogas de primeira linha utilizadas no tratamento.Texthttp://repositorio.ufes.br/handle/10/14404porUniversidade Federal do Espírito SantoDoutorado em Doenças InfecciosasPrograma de Pós-Graduação em Doenças InfecciosasUFESBRCentro de Ciências da Saúdesubject.br-rjbnDoenças Infecciosas e ParasitáriasTuberculoseDiagnósticoDormênciaLatênciaTuberculosisDiagnosisDormancyLatencyInfluência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonarInfluence of anti-tuberculosis therapy on active and dormant Mycobacterium tuberculosis present in sputum samples from patients with pulmonary tuberculosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALPedroSousadeAlmeidaJunior-2019-tese.pdfapplication/pdf934189http://repositorio.ufes.br/bitstreams/97a3e9f1-2122-4492-99a3-e29238fcb659/downloadbb10a78ee229a212d7ccc6ae6c7c67c3MD5110/144042024-08-28 15:11:04.141oai:repositorio.ufes.br:10/14404http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-10-15T17:54:48.657307Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false
dc.title.none.fl_str_mv Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
dc.title.alternative.none.fl_str_mv Influence of anti-tuberculosis therapy on active and dormant Mycobacterium tuberculosis present in sputum samples from patients with pulmonary tuberculosis
title Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
spellingShingle Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
Almeida Júnior, Pedro Sousa de
Doenças Infecciosas e Parasitárias
Tuberculose
Diagnóstico
Dormência
Latência
Tuberculosis
Diagnosis
Dormancy
Latency
subject.br-rjbn
title_short Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
title_full Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
title_fullStr Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
title_full_unstemmed Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
title_sort Influência da terapia antituberculose sobre Mycobacterium tuberculosis ativos e dormentes em amostras de escarro de pacientes com tuberculose pulmonar
author Almeida Júnior, Pedro Sousa de
author_facet Almeida Júnior, Pedro Sousa de
author_role author
dc.contributor.authorID.none.fl_str_mv https://orcid.org/
dc.contributor.authorLattes.none.fl_str_mv http://lattes.cnpq.br/9774221817421517
dc.contributor.advisor1.fl_str_mv Palaci, Moises
dc.contributor.advisor1ID.fl_str_mv https://orcid.org/0000000320136071
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2602694352713051
dc.contributor.author.fl_str_mv Almeida Júnior, Pedro Sousa de
dc.contributor.referee1.fl_str_mv Spano, Liliana Cruz
dc.contributor.referee1ID.fl_str_mv https://orcid.org/0000000262056988
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/7451382455806895
dc.contributor.referee2.fl_str_mv Santos, Kenia Valeria dos
dc.contributor.referee2ID.fl_str_mv https://orcid.org/
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/9074173162086323
dc.contributor.referee3.fl_str_mv Ribeiro, Fabiola Karla Correa
dc.contributor.referee3ID.fl_str_mv https://orcid.org/
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/9887373751252283
dc.contributor.referee4.fl_str_mv Hadad, David Jamil
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/1780085142505190
contributor_str_mv Palaci, Moises
Spano, Liliana Cruz
Santos, Kenia Valeria dos
Ribeiro, Fabiola Karla Correa
Hadad, David Jamil
dc.subject.cnpq.fl_str_mv Doenças Infecciosas e Parasitárias
topic Doenças Infecciosas e Parasitárias
Tuberculose
Diagnóstico
Dormência
Latência
Tuberculosis
Diagnosis
Dormancy
Latency
subject.br-rjbn
dc.subject.por.fl_str_mv Tuberculose
Diagnóstico
Dormência
Latência
Tuberculosis
Diagnosis
Dormancy
Latency
dc.subject.br-rjbn.none.fl_str_mv subject.br-rjbn
description Tuberculosis (TB) is one of the oldest infectious-contagious diseases in the world and the eradication of which remains a challenge. One of the major problems related to TB is the latent infection in which Mycobacterium tuberculosis (MTB) is found in its host in a metabolic state characterized as "numbness". In this state, the microorganism is not recognized by the immune system and is not detected by conventional diagnostic methods. This work aims to detect metabolically diverse populations of MTB in sputum samples of patients with pulmonary TB and to analyse the influence of tuberculosis therapy on these bacilli. The secondary objective of this study is to verify whether persistent bacilli populations may imply therapeutic failure. For this purpose, the 48 wells plate dilution technique was used, which determines the amount of microorganisms by calculating the Most Probable Number (MPN). The MPN determines the amount of microorganisms that grow in liquid medium (7H 9) and in liquid medium after the addition of liquid culture supernatant of MTB (SN). In addition, conventional diagnostic methods, bacilloscopy and solid and liquid cultures were performed. Sputum samples were collected prior to treatment (M0) and monthly until the end of treatment (M1 to M6). To lower the rate of contamination during the procedure, oral hygiene with chlorhexidine 0.12% was standardized. The preliminary clinical and epidemiological data show that the population studied is young (39.6 ± 19.4), with body mass index (BMI) within the international standards of normality (20.5 ± 1.6), being 57% male patients and 43% female. The most reported symptoms were cough and fever, with time of disease progression around 1 to 3 months as the most frequent period (71% for each). The preliminary radiographic data indicate that all patients had radiographic images suggestive of abnormal TB, with six (86%) of these patients characterized with advanced disease and one (14%) with moderate, with the same proportion found in relation to cavitation. The microbiological data reveal that only one (20%) of the conventional cultures (Ogawa or MGIT) remained positive for MTB after two months of treatment. A preliminary analysis indicated that 84% of the bacilli of the samples M0 and 98% of the M1-M4 samples are dormant or SN-dependent bacilli. When analysing the effect of TB therapy on the different MTB populations in sputum samples of patients under treatment, a progressive decrease in the amount of microorganisms over the months of treatment was observed, mainly in relation to metabolically active microorganisms.
publishDate 2019
dc.date.issued.fl_str_mv 2019-08-16
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dc.publisher.none.fl_str_mv Universidade Federal do Espírito Santo
Doutorado em Doenças Infecciosas
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dc.publisher.department.fl_str_mv Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal do Espírito Santo
Doutorado em Doenças Infecciosas
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