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Introduction The management of latent tuberculosis infection is a critical component of the World Health Organization's (WHO's) End TB Strategy. Given that between a quarter and a third of the [...], Objective To estimate of the number of children younger than 5 years who were household contacts of people with tuberculosis and were eligible for tuberculosis preventive treatment in 2017. Methods To estimate the number of eligible children, we obtained national values for the number of notified cases of bacteriologically confirmed pulmonary tuberculosis in 2017, the proportion of the population younger than 5 years in 2017 and average household size from published sources. We obtained global values for the number of active tuberculosis cases per household with an index case and for the prevalence of latent tuberculosis infection among children younger than 5 years who were household contacts of a tuberculosis case through systematic reviews, meta-analysis and Poisson regression models. Findings The estimated number of children younger than 5 years eligible for tuberculosis preventive treatment in 2017 globally was 1.27 million (95% uncertainty interval, UI: 1.24-1.31), which corresponded to an estimated global coverage of preventive treatment in children of 23% at best. By country, the estimated number ranged from less than one in the Bahamas, Iceland, Luxembourg and Malta to 350 000 (95% UI: 320 000-380 000) in India. Regionally, the highest estimates were for the World Health Organization (WHO) South-East Asia Region (510 000; 95% UI: 450 000-580 000) and the WHO African Region (470 000; 95% UI: 440 000-490 000). Conclusion Tuberculosis preventive treatment in children was underutilized globally in 2017. Treatment should be scaled up to help eliminate the pool of tuberculosis infection and achieve the End TB Strategy targets. Objectif Estimer le nombre d'enfants de moins de 5 ans qui etaient en contact avec des membres de la famille atteints de tuberculose et qui etaient eligibles a un traitement preventif de cette maladie en 2017. Methodes Pour estimer le nombre d'enfants eligibles, nous nous sommes procure, a partir de diverses publications, les valeurs nationales correspondant au nombre de cas signales de tuberculose pulmonaire confirmee par des analyses bacteriologiques en 2017, a la part de la population agee de moins de 5 ans en 2017 et a la taille moyenne des familles. Nous nous sommes procure, au moyen d'une revue systematique, d'une meta-analyse et de modeles de regression de Poisson, les valeurs mondiales correspondant au nombre de cas de tuberculose active par foyer avec cas de reference et a la prevalence de l'infection tuberculeuse latente chez les enfants de moins de 5 ans qui etaient en contact avec un membre de la famille atteint de tuberculose. Resultats Le nombre estime d'enfants de moins de 5 ans eligibles a un traitement preventif de la tuberculose dans le monde en 2017 etait de 1,27 million (intervalle d'incertitude de 95%, II: 1,24-1,31), soit une couverture mondiale de traitement preventif chez les enfants estimee a 23% au mieux. Par pays, le nombre estime allait de moins d'un aux Bahamas, en Islande, au Luxembourg et a Malte a 350 000 (II 95%: 320 000-380 000) en Inde. Au niveau des regions, les estimations les plus elevees se retrouvaient dans la Region OMS de l'Asie du Sud-Est (510 000; II 95%: 450 000-580 000) et la Region africaine de l'OMS (470 000; II 95%: 440 000-490 000). Conclusion Au niveau mondial, le traitement preventif de la tuberculose chez les enfants etait sous-utilise en 2017. Il faudrait intensifier le recours au traitement afin d'eliminer les foyers de tuberculose et d'atteindre les objectifs de la Strategie de l'OMS pour mettre fin a la tuberculose. Objetivo Estimar el numero de ninos menores de cinco anos que tuvieron contacto con personas con tuberculosis en sus hogares y que eran elegibles para el tratamiento preventivo de la tuberculosis en 2017. Metodos Para estimar el numero de ninos elegibles, se obtuvieron valores nacionales para el numero de casos notificados de tuberculosis pulmonar bacteriologicamente confirmada en 2017, la proporcion de la poblacion menor de 5 anos en 2017 y el tamano promedio del hogar de fuentes publicadas. Se obtuvieron valores globales para el numero de casos de tuberculosis activa por hogar con un caso indice y para la prevalencia de infeccion de tuberculosis latente entre los ninos menores de 5 anos que estaban en contacto con un caso de tuberculosis en el hogar mediante las revisiones sistematicas, el metanalisis y los modelos de regresion de Poisson. Resultados El numero estimado de ninos menores de 5 anos elegibles para el tratamiento preventivo de la tuberculosis en 2017 a nivel mundial fue de 1,27 millones (intervalo de incertidumbre del 95 %, IU: 1,24-1,31), lo que corresponde a una cobertura mundial estimada de tratamiento preventivo en ninos del 23 % en el mejor de los casos. Por pais, el numero estimado oscila entre menos de uno en las Bahamas, Islandia, Luxemburgo y Malta y 350 000 (95 % UI: 320 000-380 000) en la I ndia. A nivel regional, las estimaciones mas elevadas correspondieron a la Region de Asia Sudoriental de la Organizacion Mundial de la Salud (OMS) (510 000; IC del 95 %: 450 000-580 000) y a la Region Africana de la OMS (470 000; IC del 95 %: 440 000-490 000). Conclusion El tratamiento preventivo de la tuberculosis en los ninos fue utilizado muy poco a nivel mundial en 2017. El tratamiento debe ampliarse para ayudar a eliminar el conjunto de infecciones de tuberculosis y alcanzar los objetivos de la Estrategia de Fin a la Tuberculosis. [phrase omitted] 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 [...]

Background: The surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%-4.4%) of new TB patients and 18% (95% CI 7.6%-31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns.Methods and Findings: Aggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003-2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%-8.4%) among new TB patients and 11.4% (95% CI 9.4%-13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 countries (Azerbaijan, Bangladesh, Belarus, Pakistan, the Philippines, and South Africa). There were no cases of resistance to both pyrazinamide and levofloxacin among Hr-TB patients, except for the Philippines (1.8%, 95% CI 0.2-6.4) and Belarus (5.3%, 95% CI 0.1-26.0). Sequencing data for all genomic regions involved in isoniazid resistance were available for 4,563 patients. Among the 1,174 isolates that were resistant by either phenotypic testing or sequencing, 78.6% (95% CI 76.1%-80.9%) had resistance-conferring mutations in the katG gene and 14.6% (95% CI 12.7%-16.8%) in both katG and the inhA promoter region. For 6.8% (95% CI 5.4%-8.4%) of patients, mutations occurred in the inhA promoter alone, for whom an increased dose of isoniazid may be considered. The main limitations of this study are that most analyses were performed at the national rather than individual patient level and that the quality of laboratory testing may vary between countries.Conclusions: In this study, the prevalence of Hr-TB among TB patients was higher than the prevalence of rifampicin resistance globally. Many patients with Hr-TB would be missed by current diagnostic algorithms driven by rifampicin testing, highlighting the need for new rapid molecular technologies to ensure access to appropriate treatment and care. The low prevalence of resistance to pyrazinamide and fluoroquinolones among patients with Hr-TB provides further justification for the recommended modified treatment regimen. [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...

Background: Nationally representative tuberculosis (TB) prevalence surveys provide invaluable empirical measurements of TB burden but are a massive and complex undertaking. Therefore, methods that capitalize on data from these surveys are both attractive and imperative. The aim of this study was to use existing TB prevalence estimates to develop and validate an ecological predictive statistical model to indirectly estimate TB prevalence in low- and middle-income countries without survey data.Methods: We included national and subnational estimates from 30 nationally representative surveys and 2 district-level surveys in India, resulting in 50 data points for model development (training set). Ecological predictors included TB notification and programmatic data, co-morbidities and socio-environmental factors extracted from online data repositories. A random-effects multivariable binomial regression model was developed using the training set and was used to predict bacteriologically confirmed TB prevalence in 63 low- and middle-income countries across Africa and Asia in 2015.Results: Out of the 111 ecological predictors considered, 14 were retained for model building (due to incompleteness or collinearity). The final model retained for predictions included five predictors: continent, percentage retreated cases out of all notified, all forms TB notification rates per 100 000 population, population density and proportion of the population under the age of 15. Cross-fold validations in the training set showed very good average fit (R-sq = 0.92).Conclusion: Predictive ecological modelling is a useful complementary approach to indirectly estimating TB burden and can be considered alongside other methods in countries with limited robust empirical measurements of TB among the general population. [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: Recently, the tuberculosis (TB) Task Force Impact Measurement acknowledged the need to review the assumptions underlying the TB mortality estimates published annually by the World Health Organization (WHO). TB mortality is indirectly measured by multiplying estimated TB incidence with estimated case fatality ratio (CFR). We conducted a meta-analysis to estimate the TB case fatality ratio in TB patients having initiated TB treatment Methods: We searched for eligible studies in the PubMed and Embase databases through March 4th 2011 and by reference listing of relevant review articles. Main analyses included the estimation of the pooled percentages of: a) TB patients dying due to TB after having initiated TB treatment and b) TB patients dying during TB treatment. Pooled percentages were estimated using random effects regression models on the combined patient population from all studies. Main Results: We identified 69 relevant studies of which 22 provided data on mortality due to TB and 59 provided data on mortality during TB treatment. Among HIV infected persons the pooled percentage of TB patients dying due to TB was 9.2% (95% Confidence Interval (CI): 3.7%-14.7%) and among HIV uninfected persons 3.0% (95% CI: 21.2%-7.4%) based on the results of eight and three studies respectively providing data for this analyses. The pooled percentage of TB patients dying during TB treatment was 18.8% (95% CI: 14.8%-22.8%) among HIV infected patients and 3.5% (95% CI: 2.0%-4.92%) among HIV uninfected patients based on the results of 27 and 19 studies respectively. Conclusion: The results of the literature review are useful in generating prior distributions of CFR in countries with vital registration systems and have contributed towards revised estimates of TB mortality This literature review did not provide us with all data needed for a valid estimation of TB CFR in TB patients initiating TB treatment. [ABSTRACT FROM AUTHOR] more...