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Consenso , Saúde Pública , Tuberculose , Humanos , Incidência , Tuberculose/epidemiologia , Tuberculose/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Notificação de DoençasRESUMO
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: We performed an analysis of the cost and relative merits of different strategies for the diagnosis of multidrug-resistant/extensively drug-resistant TB (MDR/XDR-TB) in different settings.METHODS: We systematically reviewed the published evidence on cost/cost-effectiveness of rapid MDR/pre-XDR-TB and other methods for XDR-TB testing up to September 2022. PRISMA guidelines were followed. Collected data were analysed using Stata v17 software. Cost data were reported in USD ($) and summarised by mean, standard deviation, and range. Country income level was defined according to the World Bank country classification. Three simplified scenarios were also used to explore testing implications, based on low, intermediate and high TB incidence.RESULTS: Of 157 records, 25 studies were included with 24 reporting the cost of Xpert/RIF and two that evaluated the implementation of the MTBDRplus test. The total rapid test cost ranged from $12.41-$218, including $1.13-$74.60 for reagents/consumables and $0.40-$14.34 for equipment.CONCLUSION: The cost of MDR/XDR-TB diagnostics is lower in low resource settings. However, the cost-effective implementation of MDR/XDR-TB diagnostic algorithms requires careful consideration of local resources to avoid missed identification and the use of inappropriate regimen.
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Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Testes de Sensibilidade Microbiana , SoftwareRESUMO
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
OBJECTIVE: To evaluate care cascades for programmatic active case finding and latent TB infection (LTBI) management in young child TB contacts (aged <5 years) in Victoria, Australia. DESIGN: This was a retrospective review of public health surveillance data to identify contacts of all pulmonary TB cases notified from 2016 to 2019. RESULTS: Contact tracing identified 574 young child contacts of 251 pulmonary TB cases. Active TB was found in 28 (4.9%) contacts, none of whom had previously received bacille Calmette-Guérin vaccination, and 529 were tested for TB infection using the tuberculin skin test (TST). The overall TST positivity was 15.3% (95% CI 0.1-0.2). Among the 574 children, 150 (26.1%) were close contacts of sputum smear-positive cases and 25 (16.7%) of these were not referred to TB clinics. Of the 125 referred, 81 were considered to have LTBI, 79 agreed to commence TB preventive treatment (TPT) and 71 (89.9%) completed TPT. Following completion of TPT, no child was subsequently diagnosed with active TB. CONCLUSION: There was a high yield from active case finding and uptake of TPT. Notable losses in the cascade of care occurred around referral to tertiary clinics, but high treatment completion rates and good outcomes were found in those prescribed treatment.
OBJECTIF: Evaluer les cascades de soins pour la recherche active programmatique des cas et la prise en charge de l'infection tuberculeuse latente (ITL) chez les contacts de jeunes patients atteints de TB âgés de <5 ans dans l'état de Victoria, Australie. SCHÉMA: Revue rétrospective de données de surveillance de santé publique afin d'identifier les contacts de tous les cas de TB pulmonaire notifiés de 2016 à 2019. RÉSULTATS: Le traçage des contacts a identifié 574 jeunes enfants tous contacts de 251 cas de TB pulmonaire. Une TB active a été trouvée chez 28 enfants contacts (4,9%), aucun n'ayant reçu le vaccin bacille Calmette-Guérin, et 529 ont été testés à la recherche d'infection TB avec un test cutané à la tuberculine (TCT). La positivité d'ensemble du TCT a été de 15,3% (IC 95% 0,10,2). Parmi les 574 enfants, 150 (26,1%) étaient des contacts étroits de cas à frottis de crachats positifs et 25 (16,7%) d'entre eux n'ont pas été référés dans des structures TB. Sur les 125 enfants référés, 81 ont été considérés comme ayant une ITL, 79 ont accepté de débuter un traitement préventif (TPT) et 71 (89,9%) l'ont terminé. Aucun enfant n'a ensuite eu de diagnostic de TB active. CONCLUSION: La recherche active de cas et la couverture TPT ont eu un rendement élevé. Des pertes notables dans la cascade de soins sont survenues lors de référence aux structures tertiaires, mais ceux qui ont reçu un traitement ont eu un taux élevé d'achèvement et de bons résultats.
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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: Exposure to people with TB substantially elevates a person's risk of tuberculous infection and TB disease. Systematic screening of TB contacts enables the early detection and treatment of co-prevalent disease, and the opportunity to prevent future TB disease. However, scale-up of contact investigation in high TB transmission settings remains limited.METHODS: We undertook a narrative review to evaluate the evidence for contact investigation and identify strategies that TB programmes may consider when introducing contact investigation and management.RESULTS: Selection of contacts for priority screening depends upon their proximity and duration of exposure, along with their susceptibility to develop TB. Screening algorithms can be tailored to the target population, the availability of diagnostic tests and preventive therapy, and healthcare worker expertise. Contact investigation may be performed in the household or at communal locations. Local contact investigation policies should support vulnerable patients, and ensure that drop-out during screening can be mitigated. Ethical issues should be anticipated and addressed in each setting.CONCLUSION: Contact investigation is an important strategy for TB elimination. While its epidemiological impact will be greatest in lower-transmission settings, the early detection and prevention of TB have important benefits for contacts and their communities.
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Busca de Comunicante , Tuberculose , Características da Família , Humanos , Programas de Rastreamento , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controleAssuntos
Emigração e Imigração , Tuberculose , Humanos , Austrália/epidemiologia , Incidência , Tuberculose/epidemiologia , OcupaçõesRESUMO
Latent tuberculosis infection (LTBI) is increasingly recognised as central to programmatic TB activity, and a critical element in global progress towards TB elimination. LTBI affects a much larger group of people than active disease, who by definition are asymptomatic. Furthermore, while LTBI represents a state of risk, there remains significant uncertainty regarding which individuals will progress to active disease. Therefore, the development and implementation of LTBI management policies within the End TB Strategy requires careful ethical consideration. This article reviews ethical issues related to developments in LTBI diagnosis and management, including new tools and emerging policies and practice. Implications of LTBI management practices in specific settings are discussed, including healthcare worker infection and management of likely multidrug-resistant (MDR) LTBI. Better prediction of progression to active disease and less burdensome treatments would allow ethically appropriate expansion of testing programmes in future. However, even with existing tools there is a strong ethical imperative to provide the most effective and least burdensome therapy possible to those with LTBI, particularly those at highest risk of progression and/or poor outcomes from active disease. Greater community engagement is required in designing optimal LTBI management programmes, and ensure harms and benefits are appropriately balanced in specific settings.
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Tuberculose Latente , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológicoRESUMO
There has been a range of developments in recent years to stimulate increasing public health research activity throughout the Pacific. Development of local capacity for ethics committee review and oversight is, however, frequently underdeveloped. This is reflected in the number of Pacific Island nations where ethics committees have not been established or where only informal processes exist for ethics review and oversight. This is problematic for the optimal development of relevant and culturally appropriate research, and building up local ethics committees should be part of continued research development in the Pacific. Three areas in which local ethics committees may add value are 1) offering better capacity to reflect local priorities, 2) providing broader benefits for research capacity building, and 3) assisting to strengthen systems beyond research ethics. This article considers benefits and challenges for ethics committees in the Pacific, and suggests directions for regional development to further strengthen public health research activity.
Il y a eu toute une gamme de développements au cours des dernières années visant à stimuler un accroissement des activités de recherche en santé publique à travers la région Pacifique. Cependant, le renforcement des capacités locales de révision et de surveillance par les comités d'éthique est fréquemment sous-développé. Ceci est reflété par le nombre de nations insulaires du Pacifique où aucun comité d'éthique n'a été mis en place ou seules des procédures informelles de revue et de surveillance existent. Ceci pose un problème pour le bon développement d'une recherche pertinente et culturellement appropriée ; la mise en place de comités d'éthique locaux devrait faire partie du développement continu de la recherche dans le Pacifique. Trois domaines dans lesquels les comités d'éthique locaux pourraient avoir une valeur ajoutée sont 1) offrir une meilleure capacité de refléter les priorités locales, 2) apporter des bénéfices plus grands pour le renforcement des capacités de recherche, et 3) contribuer à renforcer les systèmes au-delà de l'éthique de la recherche. Cet article envisage les bénéfices et les défis des comités d'éthique dans le Pacifique et suggère des orientations pour le développement régional afin de développer davantage les activités de recherche en santé publique.
En los últimos años se ha observado una diversidad de progresos que estimulan las actividades de investigación en salud pública en toda la región del Pacífico. Sin embargo, la creación de competencias locales en materia de comités de ética y supervisión suele ser deficiente. Esta situación se refleja en el número de estados insulares del Pacífico que aun no cuentan con comités de ética o donde se practica solo un proceso informal de examen de los aspectos éticos y de supervisión de los estudios clínicos. Estas circunstancias representan un obstáculo al desarrollo óptimo de una investigación pertinente y culturalmente apropiada; la creación de comités de ética debe formar parte del desarrollo continuo de la investigación en el Pacífico. Estos comités aportarían ventajas en tres esferas principales, a saber: 1) una mayor capacidad de responder a las prioridades locales; 2) la ampliación de las ventajas que ofrece el fortalecimiento de la capacidad de realizar investigaciones; y 3) el mejoramiento de los sistemas de salud, más allá del terreno de la ética de la investigación. En el presente artículo se examinan las ventajas y las dificultades que presentan los comités de ética en la región del Pacífico y se proponen orientaciones para el desarrollo regional que promuevan la actividad de investigación en salud pública.
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SETTING: Victoria, Australia, is an industrialised setting with low tuberculosis (TB) incidence and universal health care. Individually tailored adherence support for self-administered daily anti-tuberculosis treatment is provided. Directly observed treatment (DOT) is very rarely used. OBJECTIVE: To review the rate of recurrent TB in Victoria between 2002 and 2014. DESIGN: This was a retrospective cohort study. All recurrent episodes of TB were reviewed and 24-locus MIRU-VNTR (mycobacterial interspersed repetitive units-variable number of tandem repeats) molecular typing was used where possible to determine the likelihood of relapse or reinfection. RESULTS: Of 4766 notifications, 32 (0.7%) were recurrent episodes. Of 20 episodes that occurred in patients who had previously completed treatment, 11 were culture-positive (0.4% of 3012 culture-positive episodes): 9 were likely relapses (distinguishable at no more than one of 24 loci) and two were likely reinfections, giving a TB relapse rate among culture-positive episodes of 52.5/100 000 person-years (mean time to study end per patient of 5.7 years). The median time until relapse was 18 months (interquartile range 12-30). CONCLUSIONS: The low rate of relapse in our setting demonstrates that individually tailored adherence support for self-administered anti-tuberculosis treatment can achieve excellent treatment outcomes.
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Antituberculosos/administração & dosagem , Adesão à Medicação , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/tratamento farmacológico , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Tipagem Molecular , Mycobacterium tuberculosis/genética , Recidiva , Estudos Retrospectivos , Autoadministração , Fatores de Tempo , Tuberculose/epidemiologia , Vitória/epidemiologiaRESUMO
SETTING: Isoniazid preventive therapy (IPT) is effective for preventing active tuberculosis (TB), although its mechanism of action is poorly understood and the optimal disease burden for IPT use has not been defined. OBJECTIVE: To describe the relationship between TB incidence and IPT effectiveness. METHODS: We constructed a model of TB transmission dynamics to investigate IPT effectiveness under various epidemiological settings. The model structure was intended to be highly adaptable to uncertainty in both input parameters and the mechanism of action of IPT. To determine the optimal setting for IPT use, we identified the lowest number needed to treat (NNT) with IPT to prevent one case of active TB. RESULTS: We found that the NNT as a function of TB incidence shows a 'U-shape', whereby IPT impact is greatest at an intermediate incidence and attenuated at both lower and higher incidence levels. This U-shape was observed over a broad range of parameter values; the optimal TB incidence was between 500 and 900 cases per 100 000 per year. CONCLUSIONS: TB burden is a critical factor to consider when making decisions about communitywide implementation of IPT. We believe that the total disease burden should not preclude programmatic application of IPT.
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Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Humanos , Incidência , Sensibilidade e Especificidade , Organização Mundial da SaúdeRESUMO
OBJECTIVE: To describe the distribution of tuberculosis (TB) and its drivers in Sheka Zone, a geographically remote region of Ethiopia. METHODS: We collected data on TB patients treated from 2010 to 2014 in the Sheka Zone. Predictors of TB incidence were determined using a multivariate generalised linear regression model. RESULTS: We found significant spatial autocorrelation of TB incidence by kebele (the smallest administrative geographical subdivision in Ethiopia) (Moran's I = 0.3, P < 0.001). The average TB incidence per kebele ranged from 0 to 453 per 100 000 population per year, and was significantly associated with average TB incidence across adjacent kebeles, TB incidence in the same kebele in the previous year and health facility availability. Each increment in TB incidence by 10/100 000/year in adjacent kebeles or in a previous year was associated with an increase in TB incidence of respectively 3.0 and 5.5/100 000/year. Availability of a health centre was associated with an increase in TB incidence of 84.3/100 000. CONCLUSIONS: TB incidence in rural Ethiopia is highly heterogeneous, showing significant spatial autocorrelation. Both local transmission and access to health care are likely contributors to this pattern. Identification of local hotspots may assist in developing and optimising effective prevention and control strategies.
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Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/transmissão , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Etiópia/epidemiologia , Feminino , Instalações de Saúde , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , População Rural , População Urbana , Adulto JovemRESUMO
Around one third of the world's population may harbour latent tuberculosis infection (LTBI), an asymptomatic immunological state that confers a heightened risk of subsequently developing tuberculosis (TB). Effectively treating LTBI will be essential if the End TB Strategy is to be realized. This review evaluates the evidence in relation to the effectiveness of preventive antibiotic therapy to treat LTBI due to both drug-susceptible and drug-resistant bacteria. Current national and international preventive therapy guidelines are summarized, as well as ongoing randomized trials evaluating regimens to prevent drug-resistant TB. Populations that may benefit most from screening and treatment for LTBI include close contacts of patients with TB (particularly children under 5 years of age) and individuals with substantial immunological impairment. The risks and benefits of treatment must be carefully balanced for each individual. Electronic decision support tools offer one way in which clinicians can help patients to make informed decisions. Modelling studies indicate that the expanded use of preventive therapy will be essential to achieving substantial reductions in the global TB burden. However, the widespread scale-up of screening and treatment will require careful consideration of cost-effectiveness, while ensuring the drivers of ongoing disease transmission are also addressed.
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Tuberculose Latente/prevenção & controle , Antituberculosos/uso terapêutico , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Humanos , Tolerância Imunológica , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/imunologia , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
SETTING: The state of Victoria, Australia, is an industrialised setting with low tuberculosis (TB) incidence, universal health care and high levels of migration. OBJECTIVE: To assess case fatality rates (CFRs) and factors associated with death in a cohort of TB cases notified between 2002 and 2013. DESIGN: Retrospective cohort study. Cases who died untreated or during treatment were reviewed to determine whether TB was a primary cause of, contributed to or was unrelated to death. Descriptive and multivariate analyses were used to compare demographic, clinical and pathological characteristics. RESULTS: Of 3956 cases, 198 (5.0%) died of any cause. TB was the primary cause of death in 99 cases (50.3%) and contributed to death in a further 34 cases, giving a TB-related CFR of 3.4%. In multivariate analysis, TB-related mortality reduced over time, and was positively associated with male sex, older age, history of substance use and disseminated or meningeal TB. Factors associated with survival included having a history of past travel to or residence in a high TB risk country, lymph node TB or extra-pulmonary TB manifestations, excluding meningeal, genitourinary, pleural and lymphnode TB. CONCLUSIONS: TB CFRs in this setting are among the lowest reported globally. TB mortality steadily decreased from 2002 to 2013.