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Abordar a tuberculose no século 21
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A Tuberculose (TB) é uma doença infeciosa, causada nos humanos pela espécie Mycobacterium tuberculosis, que afeta geralmente os pulmões, podendo também manifestar-se noutras partes do corpo. Foi identificada há mais de 70000 anos e acompanhou o êxodo do Homo sapiens desde a sua migração inicial a partir de África. Constitui assim, uma doença que nos acompanha desde essencialmente o início da história, considerada essencialmente incurável antes da descoberta dos antibióticos, resultando numa mortalidade extremamente elevada, mesmo ainda na atualidade. Após a descoberta de fármacos como a Rifampicina, Isoniazida, Pirazinamida, Etambutol e a vacina preventiva Bacillus Calmette-Guérin (BCG), esta doença deixou de ser tão temida como era, mesmo que esta ainda seja uma das principais causas de morte por doenças infeciosas. No entanto, deixou de se inovar dentro desta área durante muito tempo, continuando a ser esses os quatro fármacos de primeira linha no tratamento desta doença, e continuando também a vacina BCG a ser a única aprovada até à atualidade. Mas a realidade atual impôs uma mudança na abordagem a esta doença, devido à crescente resistência aos antibióticos, implicando um alargamento do período de tratamento, tornando assim necessário a constante procura por novos fármacos, novas estratégias terapêuticas e novas vacinas. Alguns fármacos recentes como a Delamanida, Bedaquilina e Pretomanida têm demostrado uma elevada eficácia no tratamento da TB e das estirpes multirresistentes, no entanto contínua a existir lacunas por preencher. Para além destes, o aparecimento de outros agentes que se encontram em diversas fases de desenvolvimento clínico e pré-clínico para o tratamento das estirpes resistentes, bem como a existência promissora de alguns regimes terapêuticos em estudo, evidenciam algum progresso. Apesar disto, o problema da tuberculose multirresistente permanece grave, algo agravado pelo aparecimento da pandemia global COVID-19, tendo esta um grande impacto nos acessos aos medicamentos e causando a regressão de várias das conquistas atingidas. Deste modo, surge a necessidade de maior investimento nesta área, de forma a melhor abordar o problema crescente que a TB propõe e a atingir os objetivos propostos pela OMS. Neste trabalho abordamos o estado da arte no desenvolvimento de novas terapias para a tuberculose.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis that mainly affects the lungs and can also manifest itself in other parts of the body. It was identified more than 70,000 years ago and accompanied the exodus of Homo sapiens since its initial migration from Africa. It thus constitutes a disease that has been with us since essentially the beginning of history, considered essentially incurable before the discovery of antibiotics, resulting in extremely high mortality, even today. After the discovery of drugs such as Rifampicin, Isoniazid, Pyrazinamide, Ethambutol and the preventive vaccine Bacillus Calmette-Guérin (BCG), this disease is no longer as feared as it was, even though it is still one of the main causes of death from infectious diseases. However, there was no innovation in this area for a long time, with these four drugs continuing to be first line in the treatment of this disease, and the BCG vaccine also continuing to be the only one approved to date. But the current reality required a change in the approach to this disease, due to growing resistance to antibiotics, implying an increase in the treatment period, thus making it necessary to constantly search for new medicines, new therapeutic strategies and new vaccines. Some recent medicines such as Delamanid, Bedaquiline and Pretomanid have demonstrated high efficacy in the treatment of TB and multidrug-resistant strains, however there are still gaps which need to be filled. In addition to these, the appearance of other agents that are in different phases of clinical and pre-clinical development for the treatment of resistant strains, as well as the tentative existence of some therapeutic regimes under study, show some progress. Despite this, the problem of multidrug-resistant tuberculosis remains serious, something aggravated by the emergence of the global COVID-19 pandemic, which has had a major impact on access to medicines and caused the regression of several of the acquired achievements. Therefore, there is a need for greater investment in this area, in order to better address the growing problem that TB poses and achieve the objectives proposed by the WHO. In this work we address the state of the art in the development of new therapies for tuberculosis.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis that mainly affects the lungs and can also manifest itself in other parts of the body. It was identified more than 70,000 years ago and accompanied the exodus of Homo sapiens since its initial migration from Africa. It thus constitutes a disease that has been with us since essentially the beginning of history, considered essentially incurable before the discovery of antibiotics, resulting in extremely high mortality, even today. After the discovery of drugs such as Rifampicin, Isoniazid, Pyrazinamide, Ethambutol and the preventive vaccine Bacillus Calmette-Guérin (BCG), this disease is no longer as feared as it was, even though it is still one of the main causes of death from infectious diseases. However, there was no innovation in this area for a long time, with these four drugs continuing to be first line in the treatment of this disease, and the BCG vaccine also continuing to be the only one approved to date. But the current reality required a change in the approach to this disease, due to growing resistance to antibiotics, implying an increase in the treatment period, thus making it necessary to constantly search for new medicines, new therapeutic strategies and new vaccines. Some recent medicines such as Delamanid, Bedaquiline and Pretomanid have demonstrated high efficacy in the treatment of TB and multidrug-resistant strains, however there are still gaps which need to be filled. In addition to these, the appearance of other agents that are in different phases of clinical and pre-clinical development for the treatment of resistant strains, as well as the tentative existence of some therapeutic regimes under study, show some progress. Despite this, the problem of multidrug-resistant tuberculosis remains serious, something aggravated by the emergence of the global COVID-19 pandemic, which has had a major impact on access to medicines and caused the regression of several of the acquired achievements. Therefore, there is a need for greater investment in this area, in order to better address the growing problem that TB poses and achieve the objectives proposed by the WHO. In this work we address the state of the art in the development of new therapies for tuberculosis.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Mycobacterium tuberculosis; tuberculose multirresistente; terapêutica atual da tuberculose; novos medicamentos tuberculose Tuberculose multirresistente Terapêutica atual da tuberculose Novos medicamentos tuberculose Mestrado Integrado - 2023