A systematic review of cost-utility analyses of screening methods in latent tuberculosis infection in high-risk populations.

BACKGROUND: The World Health Organisation (WHO) recommends that testing and treatment for latent tuberculosis infection (LTBI) should be undertaken in high-risk groups using either interferon gamma release assays (IGRAs) or a tuberculin skin test (TST). As IGRAs are more expensive than TST, an assessment of the cost-effectiveness of IGRAs can guide decision makers on the most appropriate choice of test for different high-risk populations. This current review aimed to provide the most up to date evidence on the cost-effectiveness evidence on LTBI testing in high-risk groups-specifically evidence reporting the costs per QALY of different testing strategies. METHODS: A comprehensive search of databases including MEDLINE, EMBASE and NHS-EED was undertaken from 2011 up to March 2021. Studies were screened and extracted by two independent reviewers. The study quality was assessed using the Bias in Economic Evaluation Checklist (ECOBIAS). A narrative synthesis of the included studies was undertaken. RESULTS: Thirty-two studies reported in thirty-three documents were included in this review. Quality of included studies was generally high, although there was a weakness across all studies referencing sources correctly and/or justifying choices of parameter values chosen or assumptions where parameter values were not available. Inclusions of IGRAs in testing strategies was consistently found across studies to be cost-effective but this result was sensitive to underlying LTBI prevalence rates. CONCLUSION: While some concerns remain about uncertainty in parameter values used across included studies, the evidence base since 2010 has grown with modelling approaches addressing the weakness pointed out in previous reviews but still reaching the same conclusion that IGRAs are likely to be cost-effective in high-income countries for high-risk populations. Evidence is also required on the cost-effectiveness of different strategies in low to middle income countries and countries with high TB burden.

Breathing Back Better! A State of the Art on the Benefits of Functional Evaluation and Rehabilitation of Post-Tuberculosis and Post-COVID Lungs.

Currently, tuberculosis (TB) and COVID-19 account for substantial morbidity and mortality worldwide, not only during their acute phase, but also because of their sequelae. This scoping review aims to describe the specific aspects of post-TB and post-COVID (long-COVID-19) sequelae, and the implications for post-disease follow-up and rehabilitation. In particular, evidence on how to identify patients affected by sequelae is presented and discussed. A section of the review is dedicated to identifying patients eligible for pulmonary rehabilitation (PR), as not all patients with sequelae are eligible for PR. Components of PR are presented and discussed, as well as their effectiveness. Other essential components to implement comprehensive rehabilitation programmes such as counselling and health education of enrolled patients, evaluation of cost-effectiveness of PR and its impact on health systems as well as research priorities for the future are included in this scoping review.

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.

Use of Monoclonal Antibody to Treat COVID-19 in Children and Adolescents: Risk of Abuse of Prescription and Exacerbation of Health Inequalities.

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies.

Multidrug and Extensively Drug-resistant Tuberculosis: Epidemiology, Clinical Features, Management and Treatment.

Multidrug-resistant tuberculosis (MDR-TB) is a growing global public health threat. MDR-TB affects more than a half-million people worldwide and is characterized by significant morbidity and mortality. New rapid diagnostic methods like GeneXpert and availability of new MDR-TB drugs and shorter treatment regimens hold promise of more patients diagnosed and put on treatment. Major challenges of lack of adequate resources, poverty, and limited access to health care continue to hamper efforts. This article reviews epidemiology, clinical features, management, and treatment, with new updates and recent changes in guidelines that offer patients better tolerated and shorter regimens for enabling therapeutic outcomes.

Prioritising children and adolescents in the tuberculosis response of the WHO European Region.

In 2017, in recognition of the challenges faced by Member States in managing childhood and adolescent tuberculosis (TB) at a country level, the WHO Regional Office for Europe held a Regional Consultation. In total, 35 countries participated in the consultations representing both high- and low-incidence Member States. Here, we provide an overview of the existing World Health Organization (WHO) documents and guidelines on childhood and adolescent TB and describe the outcomes of this regional meeting. National childhood and adolescent TB guidelines are available in 25% of Member States, while 33% reported that no such guidelines are at hand. In the majority of countries (83%), childhood and adolescent TB is part of the National Strategic Plan. The most pressing challenges in managing paediatric TB comprise the lack of adequate drug formulations, the difficult diagnosis, and treatment of presumed latent TB infection. Investments into childhood and adolescent TB need to be further advocated to achieve the End TB goals set by WHO to eliminate TB by 2030.

Tuberculosis in the European Union and European Economic Area: a survey of national tuberculosis programmes.

How many European Union (EU) and European Economic Area (EEA) countries have national tuberculosis (TB) control plans/strategies, and what are the priority actions/populations and barriers to implementation?In order to answer this question, a survey of EU/EEA national TB programme leads was undertaken.The response rate was 100% (31 countries). 55% of countries reported having a national TB strategy, all of which were in implementation; five countries were preparing a strategy. 74% had a defined organisational TB control structure with central coordination and 19% had a costed programme budget; few organisational structures included patient/civil society representation. The most frequently mentioned priority TB control actions were: reaching vulnerable population groups (80%), screening for active TB in high-risk groups (63%), implementing electronic registries (60%), contact tracing and outbreak investigation (60%), and tackling multidrug-resistant TB (60%). Undocumented migrants were the most commonly (46%) identified priority population. Perceived obstacles to implementation included barriers related to care recipients (lack of TB knowledge, treatment seeking/adherence), care providers (including need for specialist training of nurses and doctors) and health system constraints (funding, communication between healthcare and social care systems).This survey has provided an insight into TB control programmes across the EU/EEA that will inform the development of a TB strategy toolkit for member states.

Epidemiological aspects, clinical manifestations, and prevention of pediatric tuberculosis from the perspective of the End TB Strategy.

Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy.

Epidemiological aspects, clinical manifestations, and prevention of pediatric tuberculosis from the perspective of the End TB Strategy / Aspectos epidemiológicos, manifestações clínicas e prevenção da tuberculose pediátrica sob a perspectiva da Estratégia End TB

ABSTRACT Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy.

RESUMO A tuberculose continua sendo uma prioridade de saúde pública em muitos países. Em 2015, a tuberculose matou 1,4 milhão de pessoas, incluindo 210.000 crianças. Apesar dos recentes progressos no controle da tuberculose no nosso país, o Brasil ainda é um dos países com maior carga de tuberculose. Em 2015, houve 69.000 casos de tuberculose notificados no Brasil e a tuberculose foi a causa de 4.500 mortes no país. Em 2014, a Organização Mundial da Saúde aprovou a Estratégia End TB, que estabeleceu 2035 como data-alvo para atingir suas metas de redução da incidência de tuberculose em 90% e do número de mortes por tuberculose em 95%. No entanto, para alcançar essas metas no Brasil, há a necessidade de colaboração entre os diversos setores envolvidos no controle da tuberculose e de priorização de atividades, incluindo medidas de controle voltadas às populações mais vulneráveis. As crianças são altamente vulneráveis à tuberculose, e há particularidades específicas dos pacientes pediátricos quanto ao desenvolvimento da tuberculose (rápida progressão da infecção para a doença ativa), prevenção (baixa eficácia da vacinação contra as formas pulmonares e disponibilidade limitada de tratamento preventivo da infecção tuberculosa latente), diagnóstico (baixa taxa de diagnóstico confirmado bacteriologicamente); e tratamento (pouca disponibilidade de fármacos antituberculose próprios para crianças). Nesta revisão, discutimos a epidemiologia, as manifestações clínicas e a prevenção da tuberculose na infância e adolescência, destacando as peculiaridades da tuberculose ativa e latente nessas faixas etárias, a fim de promover a reflexão sobre novas abordagens para o manejo da tuberculose pediátrica no àmbito da Estratégia End TB.

Tuberculosis elimination and the challenge of latent tuberculosis.

Latent tuberculosis infection (LTBI) affects one third to one fourth of the human population and is the reservoir for a significant proportion of emerging active tuberculosis (TB) cases, especially in low incidence countries. The World Health Organization launched in 2015 the END-TB strategy that aims at TB elimination and promotes, for the first time ever, the management of LTBI. The preventive package, basically consisting of testing and treatment for LTBI in groups at high risk of reactivation, is a mainstay of the first pillar of the strategy, alongside prompt diagnosis and early treatment of both drug-susceptible and drug-resistant TB disease. Testing and treatment for LTBI should be pursued with a programmatic perspective. This implies strong political commitment, adequate funding and an effective monitoring and evaluation system. People living with HIV and children under five years of age who are household contact of a contagious TB cases are primarily targeted in all epidemiological setting. In high resource and low incidence setting, additional at risk populations should also be the target for systematic LTBI testing and treatment. Research is urgently needed to develop diagnostic tests with higher predictive value to identify individuals that progress from infection to disease. Similarly, shorter and safer treatment regimens are needed to make the trade-off between potential benefits and harms more favourable for an increasing proportion of infected individuals.

Shifting from tuberculosis control to elimination: Where are we? What are the variables and limitations? Is it achievable?

Tuberculosis (TB) is a priority in terms of incidence and mortality, with about 10.4 million new incident cases and 1.8 million deaths in 2015. The End-TB strategy recently launched by the World Health Organization in the context of the post-2015 agenda, aimed to achieve TB elimination, represents an evolution of the previous historical strategies originally aimed to achieve TB control. Globally, the current decline in TB incidence is rather slow at approximately 1,5% per year to reach the TB pre-elimination phase by 2035 (A more aggressive approach based on diagnosis and treatment of latently infected individuals has been proposed in the context of TB elimination to ensure future generations free of TB. We describes 4 scenarios which, combined, describe the TB epidemiology in a given setting: 1) in absence of interventions, 2) with early TB diagnosis and effective treatment, 3) with irregular TB treatment, 4) with TB co-infected by HIV not undergoing anti-retroviral treatment. To achieve TB Elimination, a more concerted action by funders and governments will be required for further investments into TB prevention, detection and treatment.

European policies in the management of tuberculosis among migrants.

Globally 10.4 million new tuberculosis (TB) incident cases were estimated to have occurred in 2015, of which 3% were reported in the World Health Organization European Region. Importantly, about 25% of the global multidrug-resistant TB (MDR-TB) cases are reported in the European Region, representing one of the greatest challenges to TB control; these are reported particularly in the countries of the Former Soviet Union. Over a quarter of TB cases in the European Union and European Economic Area (EU/EEA) are reported among foreign-born individuals. In line with the recent increase of migration flows towards Europe, TB among migrant populations is also on the rise, emphasizing the need for a better understanding of the TB trends at the regional and sub-regional levels, and of the existing policies on migrants and refugees. The present article is aimed at describing the policies and practices of European countries with a low and intermediate TB incidence with regard to the detection and management of TB and latent TB infection (LTBI) among refugees in Europe.