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Aims: To develop methods to disaggregate World Health Orgagnization estimates of tuberculosis (TB) incidence and mortality for each country by sex and age.Methods: For countries where incidence estimates derived from a factor adjustment of notifications and case detection ratio over 0.85, or with <1000 reported TB cases, we disaggregated incidence proportional to notifications. For each other country, a prior was constructed using a hierarchical model of age-stratified prevalence survey data, meta-analysis of sex ratios, and mathematical modelling for children under 15 years. Samples from this prior were used to disaggregate incidence and accepted if incidence exceeded notifications in each age/sex category. Results were inspected and, if implausible, incidence was disaggregated proportional to notifications. Mortality was disaggregated proportional to patterns in vital registration (VR) data in countries with VR data. Where VR data were lacking, a case-fatality ratio (CFR) approach was applied to estimated incidence, with separate CFRs by HIV/ART status, child/adult age groups, and anti-TB treatment status. Uncertainty in all disaggregated country estimates was constructed to be consistent with corresponding overall uncertainty.Results: We generated disaggregated results for 216 countries. For 125 countries, incidence disaggregation was based on notifications. Of the rest, accepted samples from the prior were considered implausible in 4 countries. For 72 countries, mortality disaggregation was based on VR data; the rest were based on the CFR approach.Conclusions: While multi-stage, this approach is comparatively simple in overall logic. Disaggregated estimates have relatively larger uncertainty and should be used with caution. [ABSTRACT FROM AUTHOR] more...

Background: Monitoring Sustainable Development Goal indicators (SDGs) and their targets plays an important role in understanding and advocating for improved health outcomes for all countries. We present the United Nations (UN) Inter-agency groups' efforts to support countries to report on SDG health indicators, project progress towards 2030 targets and build country accountability for action. Objective: We highlight common principles and practices of each Inter-agency group and the progress made towards SDG 3 targets using seven health indicators as examples. The indicators used provide examples of best practice for modelling estimates and projections using standard methods, transparent data collection and country consultations. Methods: Practices common to the UN agencies include multi-UN agency participation, expert groups to advise on estimation methods, transparent publication of methods and data inputs, use of UN-derived population estimates, country consultations, and a common reporting platform to present results. Our seven examples illustrate how estimates, using mostly Bayesian models, make use of country data to track progress towards SDG targets for 2030. Results: Progress has been made over the past decade. However, none of the seven indicators are on track to achieve their respective SDG targets by 2030. Accelerated efforts are needed, especially in low- and middle-income countries, to reduce the burden of maternal, child, communicable and noncommunicable disease mortality, and to provide access to modern methods of family planning to all women. Conclusion: Our analysis shows the benefit of UN interagency monitoring which prioritizes transparent country data sources, UN population estimates and life tables, and rigorous but replicable modelling methods. Countries are supported to build capacity for data collection, analysis and reporting. Through these monitoring efforts we support countries to tackle even the most intransient health issues, including the pandemic caused by SARS-CoV-2 that is reversing the hard-earned gains of all countries. [ABSTRACT FROM AUTHOR] more...

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions. This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs. By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with TB. [ABSTRACT FROM AUTHOR] more...

Tuberculosis (TB) was the underlying cause of 1.3 million deaths among human immunodeficiency virus (HIV)-negative people in 2016, exceeding the global number of HIV/acquired immune deficiency syndrome (AIDS) deaths. In addition, TB was a contributing cause of 374,000 HIV deaths. Despite the success of chemotherapy over the past seven decades, TB is the top infectious killer globally. In 2016, 10.4 million new cases arose, a number that has remained stable since the beginning of the 21th century, frustrating public health experts tasked to design and implement interventions to reduce the burden of TB disease worldwide. Ambitious targets for reductions in the epidemiological burden of TB have been set within the context of the Sustainable Development Goals (SDGs) and the End TB Strategy. Achieving these targets is the focus of national and international efforts, and demonstrating whether or not they are achieved is of major importance to guide future and sustainable investments. This article reviews epidemiological facts about TB, trends in the magnitude of the burden of TB and factors contributing to it, and the effectiveness of the public health response. [ABSTRACT FROM AUTHOR] more...

Background: Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases.Discussion: Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle. [ABSTRACT FROM AUTHOR] more...

Objective To assess whether the global target of halving tuberculosis (TB) mortality between 1990 and 2015 can be achieved and to conduct the first global assessment of the lives saved by the DOTS/Stop TB Strategy of the World Health Organization (WHO). Methods Mortality from TB since 1990 was estimated for 213 countries using established methods endorsed by WHO. Mortality trends were estimated separately for people with and without human immunodeficiency virus (HIV) infection in accordance with the International classification of diseases. Lives saved by the DOTS/Stop TB Strategy were estimated with respect to the performance of TB control in 1995, the year that DOTS was introduced. Findings TB mortality among HIV-negative (HIV-) people fell from 30 to 20 per 100 000 population (36%) between 1990 and 2009 and could be halved by 2015. The overall decline (when including HIV-positive [HIV+] people, who comprise 12% of all TB cases) was 19%. Between 1995 and 2009, 49 million TB patients were treated under the DOTS/Stop TB Strategy. This saved 4.6-6.3 million lives, including those of 0.23-0.28 million children and 1.4-1.7 million women of childbearing age. A further 1 million lives could be saved annually by 2015. Conclusion Improvements in TB care and control since 1995 have greatly reduced TB mortality, saved millions of lives and brought within reach the global target of halving TB deaths by 2015 relative to 1990. Intensified efforts to reduce deaths among HIV+ TB cases are needed, especially in sub-Saharan Africa. [ABSTRACT FROM AUTHOR] more...

Presents a letter to the editor about a community-based tuberculosis program in Cambodia.

Background: In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis.Methods: Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing.Findings: Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing.Interpretation: Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation.Funding: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. [ABSTRACT FROM AUTHOR] more...

Objective: To present a global update of drug-resistant tuberculosis (TB) and explore trends in 1994-2010. Methods: Data on drug resistance among new and previously treated TB patients, as reported by countries to the World Health Organization, were analysed. Such data are collected through surveys of a representative sample of TB patients or surveillance systems based on routine drug susceptibility testing. Associations between multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection and sex were explored through logistic regression. Findings: In 2007-2010, 80 countries and 8 territories reported surveillance data. MDR-TB among new and previously treated cases was highest in the Russian Federation (Murmansk oblast, 28.9%) and the Republic of Moldova (65.1%), respectively. In three former Soviet Union countries and South Africa, more than 10% of the cases of MDR-TB were extensively drug-resistant. Globally, in 1994 to 2010 multidrug resistance was observed in 3.4% (95% confidence interval, CI: 1.9-5.0) of all new TB cases and in 19.8% (95% CI: 14.4-25.1) of previously treated TB cases. No overall associations between MDR-TB and HIV infection (odds ratio, OR: 1.4; 95% CI: 0.7-3.0) or sex (OR: 1.1; 95% CI: 0.8-1.4) were found. Between 1994 and 2010, MDR-TB rates in the general population increased in Botswana, Peru, the Republic of Korea and declined in Estonia, Latvia and the United States of America. Conclusion: The highest global rates of MDR-TB ever reported were documented in 2009 and 2010. Trends in MDR-TB are still unclear in most settings. Better surveillance or survey data are required, especially from Africa and India. [ABSTRACT FROM AUTHOR] more...