Migration and medical screening for tuberculosis.

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.

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.

Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery.

OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

International collaboration among medical societies is an effective way to boost Latin American production of articles on tuberculosis / A colaboração internacional entre sociedades médicas é uma forma eficaz de aumentar a produção de artigos sobre tuberculose na América Latina

ABSTRACT 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 (MDR-TB), 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 high-quality 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.

RESUMO 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.

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis / Novos fármacos e fármacos repropostos para o tratamento da tuberculose multirresistente e extensivamente resistente

ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported.

RESUMO A tuberculose multirresistente (TB-MDR, do inglês multidrug-resistant) e a extensivamente resistente (TB-XDR, do inglês extensively drug-resistant) continuam representando um desafio para os clínicos e as autoridades de saúde pública. Infelizmente, embora haja relatos encorajadores de taxas de sucesso maiores, a taxa global de desfechos favoráveis do tratamento da TB-MDR/XDR é de apenas 54%, ou muito menor quando o espectro de resistência aos fármacos vai além do da TB-XDR. O tratamento da TB-MDR/XDR continua sendo uma tarefa difícil, em razão da alta incidência de eventos adversos, do longo tempo de tratamento, do alto culto dos esquemas utilizados e da drenagem dos recursos de saúde. Diversos ensaios e estudos foram realizados recentemente (alguns já publicados e outros em andamento), todos visando a melhorar os desfechos do tratamento da TB-MDR/XDR por meio da alteração da abordagem geral, redução do tempo de tratamento e desenvolvimento de um esquema universal. O objetivo desta revisão foi resumir o que se conseguiu até o momento, no que se refere a novos fármacos e fármacos repropostos, dando foco especial para delamanid, bedaquilina, pretomanida, clofazimina, carbapenêmicos e linezolida. Após mais de 40 anos de negligência, recentemente foi dada mais atenção á necessidade de novos fármacos para se combater a "praga branca", e resultados promissores estão sendo relatados.

Current use and acceptability of novel diagnostic tests for active tuberculosis: a worldwide survey / Uso atual e aceitabilidade de novos testes diagnósticos para tuberculose ativa: um inquérito mundial

ABSTRACT Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents), followed by molecular assays (available to 70.7%). Only a small proportion of the respondents in middle- and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4%) of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6%) and low-income countries (76.6%). The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0%) or biomarker-based serological assays (acceptable to 81.7%). Simple biomarker-based assays were more commonly deemed acceptable in middle- and low-income countries. Conclusions: Second-generation molecular assays have become more widely available in high- and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users.

RESUMO Objetivo: Determinar o uso atual e a aceitação potencial (por especialistas em tuberculose em todo o mundo) de novos testes rápidos para o diagnóstico de tuberculose que estão alinhados com os perfis de produtos alvo da Organização Mundial da Saúde. Métodos: Um inquérito multilingue foi divulgado on-line entre julho e novembro de 2016. Resultados: Um total de 723 indivíduos de 114 países respondeu ao inquérito. A baciloscopia foi o teste rápido para tuberculose mais utilizado (disponível para 90,9% dos entrevistados), seguida de ensaios moleculares (disponível para 70,7%). Apenas uma pequena proporção dos entrevistados de países de renda média e baixa tinha acesso a ensaios de liberação de IFN-γ. Imunoensaios de fluxo lateral e testes sorológicos eram utilizados por mais de um quarto dos entrevistados (25,4%). Entre os entrevistados que tinham acesso a testes moleculares, 46,7% utilizavam o teste Xpert de forma geral, sendo essa proporção maior em países de renda média baixa (55,6%) e renda baixa (76,6%). Os dados também sugerem que houve algum alinhamento de preços para testes moleculares. Os entrevistados afirmaram que aceitariam novos testes rápidos para tuberculose, se disponíveis, incluindo testes moleculares (aceitáveis para 86,0%) ou testes sorológicos baseados em biomarcadores (aceitáveis para 81,7%). Testes simples baseados em biomarcadores foram mais comumente considerados aceitáveis nos países de renda média e baixa. Conclusões: Os testes moleculares de segunda geração tornaram-se mais amplamente disponíveis em locais tanto com poucos quanto com muitos recursos. No entanto, o desenvolvimento de novos testes rápidos para tuberculose continua a ser considerado importante por especialistas em tuberculose. Nossos dados também ressaltam a necessidade de maior formação e educação dos usuários finais.

Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis? / Existe razão para reabilitação pulmonar após o tratamento quimioterápico bem-sucedido para tuberculose?

ABSTRACT The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae.

RESUMO O papel da tuberculose como uma prioridade de saúde pública e a disponibilidade de ferramentas diagnósticas para avaliar o estado funcional (espirometria, pletismografia e DLCO), a gasometria arterial, a capacidade de realizar exercícios, as lesões (radiografia de tórax e TC) e a qualidade de vida justificam o esforço de se considerar o que deve ser feito quando os pacientes completam seu tratamento. Até onde sabemos, nenhuma revisão avaliou esse tópico de forma abrangente. Nosso objetivo foi revisar as evidências disponíveis e obter algumas conclusões sobre o futuro papel da fase de "tratamento pós-tuberculose", que irá potencialmente impactar milhões de casos todos os anos. Realizou-se uma revisão não sistemática da literatura tendo como base uma pesquisa no PubMed usando palavras-chave específicas (várias combinações dos termos "tuberculose", "reabilitação", "tuberculose multirresistente", "doença pulmonar", "doença pulmonar obstrutiva", e "medidas de volume pulmonar"). As listas de referências dos artigos principais foram recuperadas para melhorar a sensibilidade da busca. Foram selecionados manuscritos escritos em inglês, espanhol e russo. As principais áreas de interesse foram sequelas de tuberculose após diagnóstico e tratamento; "pulmão destruído"; avaliação funcional das sequelas; intervenções de reabilitação pulmonar (fisioterapia, oxigenoterapia de longo prazo e ventilação); e tuberculose multirresistente. As evidências encontradas sugerem que a tuberculose é definitivamente responsável por sequelas funcionais, principalmente causando um padrão obstrutivo na espirometria (mas também padrões restritivos e mistos) e que há razão para a reabilitação pulmonar. Fornecemos também uma lista de variáveis a serem discutidas em futuros estudos sobre reabilitação pulmonar em pacientes com sequelas pós-tuberculose.

Surgery and pleuro-pulmonary tuberculosis: a scientific literature review.

Tuberculosis (TB) is still a major public health concern, mostly affecting resource-constrained settings and marginalized populations. The fight against the disease is hindered by the growing emergence of drug-resistant forms whose management can be rather challenging. Surgery may play an important role to support diagnosis and treatment of the most complex cases and improve their therapeutic outcome. We conducted a non-systematic review of the literature based on relevant keywords through PubMed database. Papers in English and Russian were included. The search was focused on five main areas of intervention as follows: (I) diagnosis of complicated cases; (II) elimination of contagious persisting cavities, despite appropriate chemotherapy; (III) treatment of destroyed lung; (V) resection of tuberculomas; (VI) treatment of tuberculous pleural empyema. Although specific practical guidelines concerning surgical indications and approaches are currently unavailable, a summary of the evidence emerged from the scientific literature was elaborated to help the clinician in the management of severely compromised TB patients. The decision to proceed to surgery is usually individualized and a careful assessment of the patient's risk profile is always recommended before performing any procedure in addition to appropriate chemotherapy.

Tuberculosis care among refugees arriving in Europe: a ERS/WHO Europe Region survey of current practices.

No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management policies among refugees in European countries.A questionnaire investigating screening and management practices among refugees was sent to 38 national TB programme representatives of low and intermediate TB incidence European countries/territories of the WHO European Region.Out of 36 responding countries, 31 (86.1%) reported screening for active TB, 19 for LTBI, and eight (22.2%) reporting outcomes of LTBI treatment. Screening for TB is based on algorithms including different combinations of symptom-based questionnaires, bacteriology and chest radiography and LTBI screening on different combinations of tuberculin skin test and interferon-γ release assays. In 22 (61.1%) countries, TB and LTBI screening are performed in refugee centres. In 22 (61.1%) countries, TB services are organised in collaboration with the private sector. 27 (75%) countries answered that screening for TB is performed as per national and international guidelines, while 19 (52.7%) gave the same answer with regards to LTBI screening. Infection control measures are inadequate in several of the countries surveyed.There is need for improved coordination of TB screening in Europe to implement the End TB Strategy and achieve TB elimination.

The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases / O desafio do tratamento da tuberculose extensivamente resistente em um hospital de referência no estado de São Paulo: um relato de três casos

ABSTRACT Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis.

RESUMO Relatamos aqui os casos de três pacientes portadores de tuberculose extensivamente resistente, internados em um hospital de referência no estado de São Paulo, e mostramos sua evolução clínica, radiológica e laboratorial pelo período de um ano. O tratamento instituído foi baseado nas diretrizes da Organização Mundial da Saúde, com a inclusão de uma nova proposta de uso de uma associação de drogas antituberculose (linezolida e imipenem). Nos casos estudados, demonstrou-se o desafio de construir um esquema terapêutico aceitável e eficiente com drogas mais tóxicas, mais dispendiosas e que foram utilizadas por períodos mais prolongados. Mostramos também o importante acréscimo nos custos do tratamento desses pacientes, com possíveis impactos no sistema de saúde mesmo após a alta hospitalar. Ressaltamos que, em casos extremos como os apresentados neste estudo, a hospitalização em centros de referência mostrou-se o caminho mais efetivo para oferecer tratamento adequado com possibilidade de cura. Em conclusão, todos os esforços dos profissionais da saúde e do poder público devem ser direcionados a evitar casos de tuberculose multirresistente e extensivamente resistente.

Rediscovering high technology from the past: thoracic surgery is back on track for multidrug-resistant tuberculosis.

The global emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB represents a core challenge for global tuberculosis control. MDR-TB and extensively drug-resistant TB are more difficult to treat and have a worse outcome compared with drug-susceptible disease. Surgery has proved to improve treatment success in MDR-TB patients. This study was designed to assess the impact of surgery in a cohort of MDR-TB patients. The authors evaluate one of the largest cohorts treated by a single center, demonstrating that specialized thoracic surgery centers may achieve excellent results with a low rate of complications after surgery, and proposing an effective model of teamwork based on pulmonologists and surgeons. A review of the evidence supporting the role of surgery in addition to chemotherapy to improve treatment outcomes in difficult-to-treat cases of TB is also performed.