Precision medicine and public health interventions: tuberculosis as a model?

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Regimens to treat multidrug-resistant tuberculosis:past, present and future perspectives

Over the past few decades, treatment of multidrug-resistant (MDR)/ extensively drugresistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 2024 months), toxicity, costs and sub-optimal outcomes. After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9-10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.</p

tuberculosis epidemiology of

Tuberculosis is a disease caused by bacilli belonging to the Mycobacterium tuberculosis complex, which includes the species Mycobacterium tuberculosis (most frequently detected in human beings), Mycobacterium africanum, and Mycobacterium bovis. It is primarily an airborne disease. Mycobacteria enter into the human airways through the inhalation of droplet nuclei, i.e., particles containing mycobacteria aerosolized by coughing, sneezing, talking, or singing. Other rare, recognized ways of transmission are the ingestion of cow milk contaminated by Mycobacterium bovis (frequent route of transmission in the past), cutaneous inoculation in laboratory workers and pathologists, and sexual intercourse [1]

No antimicrobial resistance research agenda without tuberculosis.

Commen

What Research Is Needed to Stop TB? Introducing the TB Research Movement

Christian Lienhardt and colleagues describe the development of the TB Research Movement, which aims to create a framework for concrete actions to harmonize and synergize TB research efforts globally

Implementing the global plan to stop TB, 2011-2015 - optimizing allocations and the global fund's contribution: A scenario projections study

Background: The Global Plan to Stop TB estimates funding required in low- and middle-income countries to achieve TB control targets set by the Stop TB Partnership within the context of the Millennium Development Goals. We estimate the contribution and impact of Global Fund investments under various scenarios of allocations across interventions and regions. Methodology/Principal Findings: Using Global Plan assumptions on expected cases and mortality, we estimate treatment costs and mortality impact for diagnosis and treatment for drug-sensitive and multidrug-resistant TB (MDR-TB), including antiretroviral treatment (ART) during DOTS for HIV-co-infected patients, for four country groups, overall and for the Global Fund investments. In 2015, China and India account for 24% of funding need, Eastern Europe and Central Asia (EECA) for 33%, sub-Saharan Africa (SSA) for 20%, and other low- and middle-income countries for 24%. Scale-up of MDR-TB treatment, especially in EECA, drives an increasing global TB funding need - an essential investment to contain the mortality burden associated with MDR-TB and future disease costs. Funding needs rise fastest in SSA, reflecting increasing coverage need of improved TB/HIV management, which saves most lives per dollar spent in the short term. The Global Fund is expected to finance 8-12% of Global Plan implementation costs annually. Lives saved through Global Fund TB support within the available funding envelope could increase 37% if allocations shifted from current regional demand patterns to a prioritized scale-up of improved TB/HIV treatment and secondly DOTS, both mainly in Africa - with EECA region, which has disproportionately high per-patient costs, funded from alternative resources. Conclusions/Significance: These findings, alongside country funding gaps, domestic funding and implementation capacity and equity considerations, should inform strategies and policies for international donors, national governments and disease control programs to implement a more optimal investment approach focusing on highest-impact populations and interventions

Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives.

Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20-24 months), toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9-10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB

Tuberculosis in the Western Pacific Region: Estimating the burden of disease and return on investment 2020–2030 in four countries

Background: We aimed to estimate the disease burden of Tuberculosis (TB) and return on investment of TB care in selected high-burden countries of the Western Pacific Region (WPR) until 2030. Methods: We projected the TB epidemic in Viet Nam and Lao People's Democratic Republic (PDR) 2020–2030 using a mathematical model under various scenarios: counterfactual (no TB care); baseline (TB care continues at current levels); and 12 different diagnosis and treatment interventions. We retrieved previous modeling results for China and the Philippines. We pooled the new and existing information on incidence and deaths in the four countries, covering >80% of the TB burden in WPR. We estimated the return on investment of TB care and interventions in Viet Nam and Lao PDR using a Solow model. Findings: In the baseline scenario, TB incidence in the four countries decreased from 97•0/100,000/year (2019) to 90•1/100,000/year (2030), and TB deaths from 83,300/year (2019) to 71,100/year (2030). Active case finding (ACF) strategies (screening people not seeking care for respiratory symptoms) were the most effective single interventions. Return on investment (2020–2030) for TB care in Viet Nam and Lao PDR ranged US$4-US$49/dollar spent; additional interventions brought up to US$2•7/dollar spent. Interpretation: In the modeled countries, TB incidence will only modestly decrease without additional interventions. Interventions that include ACF can reduce TB burden but achieving the End TB incidence and mortality targets will be difficult without new transformational tools (e.g. vaccine, new diagnostic tools, shorter treatment). However, TB care, even at its current level, can bring a multiple-fold return on investment

The health workforce crisis in TB control: a report from high-burden countries

BACKGROUND: Human resources (HR) constraints have been reported as one of the main barriers to achieving the 2005 global tuberculosis (TB) control targets in 18 of the 22 TB high-burden countries (HBCs); consequently we try to assess the current HR available for TB control in HBCs. METHODS: A standard questionnaire designed to collect information on staff numbers, skills, training activities and current staff shortages at different health service levels was sent to national TB control programme managers in all HBCs. RESULTS: Nineteen HBCs (86%) replied, and 17 (77%) followed the questionnaire format to provide data. Complete information on staff numbers at all service levels was available from nine countries and data on skill levels and training were complete in six countries. Data showed considerable variations in staff numbers, proportions of trained staff, length of courses and quality of training activities. Eleven HBCs had developed training materials, many used implementation guidelines for training and only three used participatory educational methods. Two countries reported shortages of staff at district health facility level, whereas 14 reported shortages at central level. There was no apparent association between reported staff numbers (and skills) and the country's TB burden or current case detection rates (CDR). CONCLUSION: There were few readily available data on HR for TB control in HBCs, particularly in the larger ones. The great variations in staff numbers and the poor association between information on workforce, proportion of trained staff, and length and quality of courses suggested a lack of valid information and/or poor data reliability. There is urgent need to support HBCs to develop a comprehensive HR strategy involving short-term and long-term HR development plans and strengthening their HR planning and management capabilities

Multidrug-resistant Tuberculosis Management in Resource-limited Settings

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings