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In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps.
En 2022, la Région européenne de l'OMS a recensé 15,1% de l'ensemble des cas de TB résistante à la rifampicine/multirésistante aux médicaments (RR/MDR-TB). La majorité de ces cas ont eu lieu dans 18 pays hautement prioritaires d'Europe orientale et d'Asie centrale, parmi lesquels de nombreux ont adhéré à une initiative dirigée par le Bureau régional de l'OMS pour l'Europe. L'objectif était de mettre en place trois schémas thérapeutiques modifiés plus courts de 9 mois, entièrement oraux, (mSTR, pour l'anglais "fully oral, 9-month modified shorter treatment regimens ¼) pour le traitement de la RR/MDR-TB dans le cadre d'une recherche opérationnelle. Ces trois schémas étaient les suivants 1) bédaquiline + linézolide + lévofloxacine + clofazimine + cyclosérine (BdqLzdLfxCfzCs) ; 2) BdqLzdLfxCfz + delamanid (Dlm) pour les enfants de plus de 6 ans et les adultes ; et 3) DlmLzdLfxCfz pour les enfants de moins de 6 ans. Le projet visait à améliorer l'efficacité des traitements, à faciliter l'application des mSTR, à promouvoir la qualité des soins et à renforcer les capacités de recherche, tout en contribuant aux connaissances mondiales sur l'utilisation des mSTR par voie orale. Entre avril 2020 et juin 2022, plus de 2 800 patients ont reçu un traitement par mSTR dans la Région Européenne de l'OMS. Cette expérience unique a encouragé la continuation de la collaboration avec les programmes nationaux de lutte contre la TB, les autorités sanitaires, les experts et les donateurs tant en Europe qu'à l'étranger. L'accent est mis sur la mise en Åuvre de la recherche opérationnelle et l'amélioration de la qualité des soins dans les pays de la région où la TB est fortement prévalente. Nous avons détaillé les principes de l'initiative, ses avantages et ses inconvénients, dans l'espoir d'inciter d'autres pays à suivre cet exemple, tout en exposant les étapes à venir.
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BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
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Tuberculose , Humanos , Bancos de Espécimes Biológicos , Tuberculose/tratamento farmacológico , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
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Tuberculose Meníngea , Adolescente , Criança , Humanos , Tuberculose Meníngea/tratamento farmacológico , Padrão de Cuidado , Técnica Delphi , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipersensibilidade , Tuberculose , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Pessoal de SaúdeRESUMO
BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015-2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0-82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.
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Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Rifampina/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Organização Mundial da SaúdeAssuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/uso terapêutico , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Fumar/efeitos adversos , Fumar/epidemiologia , Resultado do Tratamento , IsoniazidaRESUMO
BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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Antituberculosos , Monitoramento de Medicamentos , Tuberculose , Humanos , Assistência ao Paciente , Padrões de Referência , Tuberculose/tratamento farmacológico , Antituberculosos/administração & dosagemRESUMO
BACKGROUND: As the WHO European Region has the highest proportion of multidrug-resistant TB (MDR-TB) among total incident TB cases, many children and adolescents are at risk of MDR-TB infection and disease.METHODS: We performed an electronic survey of clinicians and TB programme personnel who attended the 2020 Regional Consultation on child and adolescent TB organised by the WHO Regional Office. We characterised access to diagnostics and drugs, and practices in the prevention and management of child and adolescent MDR-TB.RESULTS: Children and adolescents are inconsistently represented in national guidelines and budgets; child-friendly drug formulations for MDR-TB treatment are insufficiently available in 57% of countries, and 32% of countries reported paediatric drug stock-outs. The novel drugs, bedaquiline and delamanid, are accessible by respectively 80% and 60% of respondent countries. Respondents were asked how many children were diagnosed with MDR-TB in 2019, and a comparison of this number to modelled estimates of incidence (to identify the case detection gap) and WHO notifications (to identify the case reporting gap) showed substantial differences in both comparisons.CONCLUSIONS: Better representation of this patient group in guidelines and budgets, greater access to drugs and improved reporting are essential to reach TB elimination in this Region.
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Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Adolescente , Antituberculosos/uso terapêutico , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Organização Mundial da SaúdeRESUMO
BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.
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Tuberculose Latente , Tuberculose , Cuidadores , Criança , Humanos , Programas de Rastreamento , Padrões de Referência , Tuberculose/diagnóstico , Tuberculose/prevenção & controleRESUMO
BACKGROUND: Distinguishing TB relapse from re-infection is important from a clinical perspective to document transmission patterns. We investigated isolates from patients classified as relapse to understand if these were true relapses or re-infections. We also investigated shifts in drug susceptibility patterns to distinguish acquired drug resistance from re-infection with resistant strains.METHODS: Isolates from pulmonary TB patients from 2009 to 2017 were analysed using whole-genome sequencing (WGS).RESULTS: Of 11 patients reported as relapses, WGS results indicated that 4 were true relapses (single nucleotide polymorphism difference ≤5), 3 were re-infections with new strains, 3 were both relapse and re-infection and 1 was a suspected relapse who was later categorised as treatment failure based on sequencing. Of the 9 patients who went from a fully susceptible to a resistant profile, WGS showed that none had acquired drug resistance; 6 were re-infected with new resistant strains, 1 was probably infected by at least two different genotype strains and 2 were phenotypically misclassified.CONCLUSIONS: WGS was shown to distinguish between relapse and re-infection in an unbiased way. The use of WGS minimises the risk of false classification of treatment failure instead of re-infection. Furthermore, our study showed that strains without major genetic differences can cause re-infection.
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Mycobacterium tuberculosis , Tuberculose Pulmonar , Antituberculosos/uso terapêutico , Genótipo , Humanos , Mycobacterium tuberculosis/genética , Recidiva , Reinfecção , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.
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Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Nitroimidazóis/uso terapêutico , Oxazóis/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
BACKGROUND: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). OBJECTIVES: To verify the differences in TB and HIV services in EE vs. WE. METHODS: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. RESULTS: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. CONCLUSION: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.
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Infecções por HIV , Tuberculose , Antituberculosos/uso terapêutico , Atenção à Saúde , Europa (Continente)/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
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Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Antituberculosos/uso terapêutico , Criança , Protocolos Clínicos , Humanos , Rifampina/uso terapêutico , Fatores de Tempo , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
BACKGROUND: Using 2004-2007 TB:HIV Study data
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Coinfecção , Infecções por HIV , Mycobacterium tuberculosis , Tuberculose , Antituberculosos/uso terapêutico , Coinfecção/tratamento farmacológico , Atenção à Saúde , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , América Latina/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Modelos de Riscos Proporcionais , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
The role of mutations in genes associated with phenotypic resistance to bedaquiline (BDQ) and delamanid (DLM) in Mycobacterium tuberculosis complex (MTBc) strains is poorly characterized. A clear understanding of the genetic variants' role is crucial to guide the development of molecular-based drug susceptibility testing (DST). In this work, we analyzed all mutations in candidate genomic regions associated with BDQ- and DLM-resistant phenotypes using a whole-genome sequencing (WGS) data set from a collection of 4,795 MTBc clinical isolates from six countries with a high burden of tuberculosis (TB). From WGS analysis, we identified 61 and 163 unique mutations in genomic regions potentially involved in BDQ- and DLM-resistant phenotypes, respectively. Importantly, all strains were isolated from patients who likely have never been exposed to these medicines. To characterize the role of mutations, we calculated the free energy variation upon mutations in the available protein structures of Ddn (DLM), Fgd1 (DLM), and Rv0678 (BDQ) and performed MIC assays on a subset of MTBc strains carrying mutations to assess their phenotypic effect. The combination of structural and phenotypic data allowed for cataloguing the mutations clearly associated with resistance to BDQ (n = 4) and DLM (n = 35), only two of which were previously described, as well as about a hundred genetic variants without any correlation with resistance. Significantly, these results show that both BDQ and DLM resistance-related mutations are diverse and distributed across the entire region of each gene target, which is of critical importance for the development of comprehensive molecular diagnostic tools.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Diarilquinolinas/farmacologia , Genômica , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Nitroimidazóis , Oxazóis , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
The revised edition of the WHO's Ethics Guidance for the Implementation of the TB Strategy has added a new chapter on compassionate use (CU) and expanded access (EA) to TB drugs. CU and EA programmes authorise access to drugs that have not yet received marketing approval outside of clinical trials. They are aimed at allowing researchers access to investigational drugs in the absence of complete evidence of efficacy and safety to patients with multidrug-resistant (MDR) or rifampicin-resistant TB (RR-TB) when no other treatment options are available. In doing so, the guidance acknowledged the urgent necessity to offer these patients all possible treatments in respect of considerations of justice, human rights, human dignity, autonomy of the individual and protection of the community. Regulators are in general willing to accept a higher level of uncertainty in the risk-benefit assessment of medicines for life-threatening diseases when there is an unmet medical need. This attests to a paradigm change, which this article argues should also apply to allow for effective access to experimental TB medicines. Furthermore, in this article, we analyse the challenges connected to the establishment of a secure and effective regime of access to experimental drugs in the context of MDR/RR-TB as well as the ethical principles and human rights arguments in favour of the development of such programmes.
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Pesquisa Biomédica , Tuberculose Resistente a Múltiplos Medicamentos , Ensaios de Uso Compassivo , Drogas em Investigação , Humanos , Justiça Social , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
The World Health Organization (WHO) defines palliative care as the prevention and relief of the physical, psychological, social and spiritual suffering of adults and children with life-threatening illnesses and psycho-social support for their families. Palliative care and symptom relief (PCSR) also addresses suffering in nonlife-threatening situations such as after cure. PCSR should never be considered a substitute for tuberculosis (TB) prevention and treatment, but should be accessible by everyone in need. PCSR can reduce suffering and improve quality of life of patients with end-stage chronic illnesses while reducing costs for health care systems and providing financial risk protection for patients' families. It also may help enable patients to adhere to long and noxious treatments and thereby reduce mortality and help protect public health. Basic PCSR can be taught easily to TB specialists as well as primary care clinicians and delivered in hospitals, clinics or patients' homes combined with infection control. For these reasons, integration of PCSR into multidrug-resistant (MDR) and extensively drug-resistant TB (XDR-TB) treatment programs is medically and morally imperative. We propose an essential package of PCSR for people with M/XDR-TB that includes a set of safe, effective and inexpensive medicines and equipment, social supports for patients and caregivers living in extreme poverty, and necessary human resources. The package aligns with WHO guidance on programmatic management of drug-resistant (DR) TB and should be universally accessible by people affected by M/XDR-TB. We also describe the ethical practice of PCSR for people with M/XDR-TB and identify needed areas of research in PCSR for people with M/XDR-TB.
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Antituberculosos/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Cuidados Paliativos/métodos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/fisiopatologia , Humanos , Adesão à Medicação , Qualidade de Vida , Apoio Social , Tuberculose Resistente a Múltiplos Medicamentos/fisiopatologiaRESUMO
As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed.
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Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Criança , Europa (Continente) , Humanos , Equipe de Assistência ao PacienteRESUMO
BACKGROUND: For the first time in almost 50 years, there are new drugs available for the treatment of tuberculosis (TB), including bedaquiline (BDQ) and delamanid (DLM). The rate of introduction, however, has not kept pace with patient needs. It is estimated that as many as 23% of multidrug-resistant TB (MDR-TB) patients have an indication for receiving BDQ. As this is the first time the MDR-TB community is introducing new medications, it is important to understand how implementation can be developed in a variety of settings. METHODS: A qualitative assessment of country TB programs in which more than 5% of MDR-TB patients were started on BDQ under program conditions. RESULTS: National TB programs in Belarus, France, Georgia, South Africa, and Swaziland all started sizeable cohorts of patients on BDQ in 2015. Common factors observed in these programs included experience with compassionate use/expanded access, support from implementing partners, and adequate national or donor-supported budgets. Barriers to introduction included restriction of BDQ to the in-patient setting, lack of access to companion drugs, and the development of systems for pharmacovigilance. CONCLUSION: The five countries in this paper are examples of the introduction of new therapeutic options for the treatment of TB.