Bedaquiline and multidrug-resistant tuberculosis: a systematic and critical analysis of the evidence

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Multiresistentse tuberkuloosi ravi kulutulusus ja ravitulemused erinevate ravistrateegiate rakendamisel

Järjest laialdasemalt rakendatakse multiresistentse tuberkuloosi haigete raviks DOTS-Plus strateegiat, kasutades teise rea ravimeid, kuid teadmised nende efektiivsuse ja kulutulususe kohta on vähesed. Uuringus hinnati alates 2001. a augustist Eestis rakendatud DOTS-Plus strateegia tõhusust, maksumust ja kulutulusust võrreldes 3 alternatiivset ravi strateegiat: DOTS-Plus strateegia, pre-DOTS-plus strateegia ja DOTS-strateegia. Kulud arvutati 2002. a kehtinud hindades, tõhususe näitajateks olid tuberkuloosist põhjustatud surmade arv, kaotatud haiguskoormus ja kulutulususe näitajaks säästetud haiguskoormuse maksumus. Saadud andmete alusel võib väita, et kasutades DOTS-Plus strateegiat, on võimalik oluliselt paran dada multiresistentse tuberkuloosi haigete ravitulemusi ning võrreldes teiste võimalustega on see kulutulusaim. Eesti Arst 2006; 85 (3): 148–15

Do we need a new Fleming époque: The nightmare of drug-resistant tuberculosis.

Tuberculosis represents an important clinical and public health problem globally, particularly in low- and middle-income countries. During the last 20 years, two relevant events has changed the epidemiology of the disease: the spread of the TB/HIV co-infection and the emergence and spread of the multi-drug resistance tuberculosis (i.e., tuberculosis caused by strains resistant to at least isoniazid and rifampicin). The latter phenomenon has been generated by the inappropriate management of the anti-tuberculosis drugs. Currently, the World Health Organization estimates at least 600,000 MDR-TB cases worldwide, particularly in China, India, South Africa, and in former Soviet Union countries. Unfortunately, new difficult-to-treat MDR-TB cases have been described, named XDR- or TDR-TB (extensively or totally drug-resistant tuberculosis, respectively). Numerous observational retrospective studies proved the poorer prognostic profile of the MDR-TB cases when compared with drug-susceptible tuberculosis. The clinical management of the patients with an XDR and beyond pattern is complicated owing to the poorest, expensive, and toxic therapeutic options. MDR-TB is currently under-reported because of methodological issues, mainly related to the poor proficiency of laboratory testing. National public health strategies should reduce the increase of tuberculosis cases without therapeutic alternatives. Furthermore, research and development activities, based on continuous and sustained funding, should be improved, together with the implementation and the scale-up of effective infection control measures in healthcare settings and in the community. © 2013 Asian-African Society for Mycobacteriology

Pulmonary Tuberculosis Management: 2015 Update

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Drug resistant TB - latest developments in epidemiology, diagnostics and management

AIM: The aim of this review is to inform the reader on the latest developments in epidemiology, diagnostics and management. EPIDEMIOLOGY: Drug-resistant Tuberculosis (DR-TB) continues to be a current global health threat, and is defined by higher morbidity and mortality, sequelae, higher cost and complexity. The WHO classifies drug-resistant TB into 5 categories: isoniazid-resistant TB, rifampicin resistant (RR)-TB and MDR-TB, (TB resistant to isoniazid and rifampicin), pre-extensively drug-resistant TB (pre-XDR-TB) which is MDR-TB with resistance to a fluoroquinolone and finally XDR-TB that is TB resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). Of 500,000 estimated new cases of RR-TB in 2020, only 157 903 cases are notified. Only about a third of cases are detected and treated annually. DIAGNOSTICS: Recently newer rapid diagnostic methods like the GeneXpert, whole genome sequencing and Myc-TB offer solutions for rapid detection of resistance. TREATMENT: The availability of new TB drugs and shorter treatment regimens have been recommended for the management of DR-TB. CONCLUSION: Despite advances in diagnostics and treatments we still have to find and treat two thirds of the drug resistant cases that go undetected and therefore go untreated each year. Control of TB and elimination will only occur if cases are detected, diagnosed and treated promptly

Imigração e triagem médica para tuberculose

Vulnerable populations, such as migrants and refugees, have an increased risk of tuberculosis disease, especially in the first years after arrival in the host country. The presence of migrants and refugees in Brazil exponentially grew over the period between 2011 and 2020, and approximately 1.3 million migrants from the Global South were estimated to be residing in Brazil, most of whom from Venezuela and Haiti. Tuberculosis control programs for migrants can be divided into pre- and post-migration screening strategies. Pre-migration screening aims to identify cases of tuberculosis infection (TBI) and can be carried out in the country of origin (pre-entry) or in the destination country (at entry). Pre-migration screening can also detect migrants at an increased risk of developing tuberculosis in the future. High-risk migrants are then followed up in post-migration screening. In Brazil, migrants are considered a priority group for the active search for tuberculosis cases. However, there is no recommendation or plan regarding screening for TBI in migrants and refugees. Ensuring prevention, diagnosis, and treatment for TBI and tuberculosis disease in migrant populations is an important aspect of tuberculosis control and elimination. In this review article, we address epidemiological aspects and access to health care for migrants in Brazil. In addition, the migration medical screening for tuberculosis was reviewed.Populações vulneráveis, como imigrantes e refugiados, apresentam maior risco de tuberculose doença, especialmente nos primeiros anos após a chegada ao país de acolhimento. A presença de imigrantes e refugiados no Brasil cresceu exponencialmente no período entre 2011 e 2020, sendo estimado que aproximadamente 1,3 milhão de imigrantes do Sul Global residiam no Brasil, a maioria proveniente da Venezuela e do Haiti. Os programas de controle da tuberculose para imigrantes podem ser divididos em estratégias de triagem pré- e pós-migração. A triagem pré-migração visa identificar casos de tuberculose infecção (TBI) e pode ser realizada no país de origem (pré-entrada) ou no país de destino (no momento da entrada). A triagem pré-migração também pode detectar imigrantes com maior risco de desenvolver tuberculose no futuro. Os imigrantes de alto risco são então acompanhados na triagem pós-migração. No Brasil, os imigrantes são considerados um grupo prioritário para a busca ativa de casos de tuberculose. No entanto, não há recomendação ou plano sobre triagem para TBI em imigrantes e refugiados. Garantir a prevenção, o diagnóstico e o tratamento da TBI e da tuberculose doença em populações imigrantes é um aspecto importante do controle e eliminação da tuberculose. Neste artigo de revisão, abordamos aspectos epidemiológicos e acesso à saúde para imigrantes no Brasil. Além disso, revisou-se a triagem médica de imigrantes para tuberculose

A colaboração internacional entre sociedades médicas é uma forma eficaz de aumentar a produção de artigos sobre tuberculose na América Latina

Objective: Most studies of tuberculosis originate from high-income countries with a low incidence of tuberculosis. A review of the scientific production on tuberculosis in Latin American countries, most of which are low- or middle-income countries (some with high or intermediate tuberculosis incidence rates), would improve the understanding of public health challenges, clinical needs, and research priorities. The aims of this systematic review were to determine what has been published recently in Latin America, to identify the leading authors involved, and to quantify the impact of international collaborations. Methods: We used PubMed to identify relevant manuscripts on pulmonary tuberculosis (PTB), drug-resistant tuberculosis (DR-TB), or multidrug-resistant tuberculosis (MDRTB), published between 2013 and 2018. We selected only studies conducted in countries with an annual tuberculosis incidence of ≥ 10,000 reported cases and an annual MDR-TB incidence of ≥ 300 estimated cases, including Brazil, Peru, Mexico, Colombia, and Argentina. Articles were stratified by country, type, and topic. Results: We identified as eligible 395 studies on PTB and 188 studies on DR/MDR-TB—of which 96.4% and 96.8%, respectively, were original studies; 35.5% and 32.4%, respectively, had an epidemiological focus; and 52.7% and 36.2%, respectively, were conducted in Brazil. The recent Latin American Thoracic Association/European Respiratory Society/ Brazilian Thoracic Association collaborative project boosted the production of highquality articles on PTB and DR/MDR-TB in Latin America. Conclusions: Most of the recent Latin American studies on tuberculosis were conducted in Brazil, Mexico, or Peru. Collaboration among medical societies facilitates the production of scientific papers on tuberculosis. Such initiatives are in support of the World Health Organization call for intensified research and innovation in tuberculosis.Objetivo: A maioria dos estudos sobre tuberculose é proveniente de países de alta renda com baixa incidência de tuberculose. Uma revisão da produção científica sobre tuberculose na América Latina, região onde a maioria dos países é de baixa ou média renda, alguns com alta ou média incidência de tuberculose, seria útil para entender as necessidades clínicas e de saúde pública, bem como as prioridades de pesquisa. O objetivo desta revisão sistemática foi identificar o que foi publicado recentemente na América Latina, os principais autores envolvidos e o impacto das colaborações internacionais. Métodos: O PubMed foi usado para identificar manuscritos relevantes sobre tuberculose pulmonar (TBP) e tuberculose resistente ou multirresistente publicados entre 2013 e 2018. Foram selecionados apenas os estudos realizados em países com incidência anual de tuberculose ≥ 10.000 casos notificados e incidência anual de tuberculose multirresistente ≥ 300 casos estimados, incluindo Brasil, Peru, México, Colômbia e Argentina. Os artigos foram estratificados por país, tipo e tópico. Resultados: Foram identificados 395 estudos sobre TBP e 188 sobre tuberculose resistente/multirresistente, dos quais 96,4% e 96,8%, respectivamente, eram estudos originais; 35,5% e 32,4%, respectivamente, concentravam-se em epidemiologia; 52,7% e 36,2%, respectivamente, haviam sido realizados no Brasil. O recente projeto colaborativo da Asociación Latinoamericana de Tórax/European Respiratory Society/Sociedade Brasileira de Pneumologia e Tisiologia impulsionou a produção de artigos de alta qualidade sobre TBP e tuberculose resistente/ multirresistente na América Latina. Conclusões: A maioria dos estudos recentes sobre tuberculose na América Latina foi realizada no Brasil, México ou Peru. A colaboração entre sociedades médicas facilita a produção de artigos científicos sobre tuberculose. Iniciativas assim atendem ao pedido da Organização Mundial da Saúde de intensificação das pesquisas e inovações na área de tuberculose

Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts

OBJECTIVE: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. METHODS: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. RESULTS: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. CONCLUSIONS: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients

post tuberculosis treatment infectious complications

Following greater attention and follow-up of patients with treated pulmonary tuberculosis (TB), it has emerged that infections are more likely to occur in this cohort of patients. This comes as no surprise, as pulmonary TB is a destructive process that leads to cicatrization, alteration of parenchyma, bronchiectasis, and scarring of the lung, with reduction of lung volumes and an impact on pulmonary function. In addition to relapse and re-infection with TB, other pathogens are increasingly recognized in post-TB patients. This paper serves as a summary and guide on how to approach the post-TB patient with new signs and symptoms of pulmonary infection in order to ensure optimal management and rehabilitation. Keywords: Tuberculosis, Post-treatment complication, Sequelae, Pulmonary rehabilitation, NTM, Bronchiectasi

Sequelas pulmonares da tuberculose : comparação de coortes do Brasil, Itália e México

Objective: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.Objetivo: Avaliar a função pulmonar em uma coorte de pacientes com história de tuberculose pulmonar no Brasil, bem como avaliar o declínio da função pulmonar ao longo do tempo e compará-lo com o observado em coortes semelhantes no México e Itália. Métodos: As três coortes foram comparadas quanto à idade, tabagismo, testes de função pulmonar, teste de caminhada de seis minutos e gasometria arterial. Na coorte brasileira, os resultados dos testes de função pulmonar, do teste de caminhada de seis minutos e da gasometria arterial logo após o término do tratamento da tuberculose foram comparados com os obtidos no fim do período de acompanhamento. Resultados: As três coortes foram muito diferentes quanto aos resultados dos testes de função pulmonar. Os padrões ventilatórios mais comuns nas coortes brasileira, italiana e mexicana foram o padrão obstrutivo, o padrão misto e o padrão normal [em 58 pacientes (50,9%), em 18 pacientes (41,9%) e em 26 pacientes (44,1%), respectivamente]. Apenas 2 casos de tuberculose multirresistente foram incluídos na coorte brasileira, ao passo que na coorte mexicana foram incluídos 27 casos (45,8%). As médias da PaO2 e SaO2 foram mais baixas na coorte mexicana do que na brasileira (p < 0,0001 e p < 0,002 para PaO2 e SaO2 , respectivamente). Na coorte brasileira, quase todos os parâmetros funcionais se deterioraram ao longo do tempo. Conclusões: Este estudo reforça a importância do tratamento precoce e eficaz de pacientes com tuberculose sensível, pois a tuberculose multirresistente aumenta o dano pulmonar. Quando o tratamento da tuberculose é concluído, os pacientes devem ser avaliados o quanto antes e, caso se estabeleça o diagnóstico de sequelas pulmonares da tuberculose, é preciso tratá-los e oferecer-lhes reabilitação pulmonar, pois há evidências de que ela é eficaz nesses pacientes