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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], 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 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. [TEXT NOT REPRODUCIBLE IN ASCII.] Surveillance de la resistance aux medicaments antituberculeux dans le monde: une analyse actualisee, 2007-2010 Objectif Presenter une mise a jour globale de la tuberculose (TB) pharmacoresistante et explorer les tendances de 1994 a 2010. Methodes Les donnees relatives a la resistance aux medicaments des nouveaux patients de TB et de ceux traites anterieurement, telles que rapportees par les pays a l'Organisation mondiale de la Sante, ont ete analysees. Ces donnees sont recueillies par des enquetes representatives aupres des patients ou des systemes de surveillance bases sur des tests systematiques de sensibilite. Les associations entre la tuberculose ultraresistante (TB-UR), le virus de l'immunodeficience humaine (VIH) et le sexe ont ete explorees par regression logistique. Resultats En 2007-2010, 80 pays et 8 territoires ont fourni des donnees de surveillance. Parmi les cas nouveaux et traites a nterieurement, la TB-UR etait la plus elevee dans la Federation de Russie (oblast de Mourmansk, 28,9%) et la Republique de Moldavie (65,1%), respectivement. Dans trois pays de l'ex-Union sovietique et en Afrique du Sud, plus de 10% des cas deTB-UR etaient ultra-resistants. Globalement, en 1994-2010, la multiresistance aux medicaments a ete observee chez 3,4% (intervalle de confiance 95%, IC: 1,9 a 5,0) de tous les nouveaux cas de TB et 19,8% (IC 95%: 14,4 a 25,1) des cas de TB traites anterieurement. Aucune association generale entre la TB-UR et l'infection au VIH (rapports de cotes, OR: 1,4, IC 95%: 0,7 a 3,0) ou le sexe (OR: 1,1, IC 95%: 0,8 a 1,4) n'a ete trouvee. Entre 1994 et 2010, les taux de TB-UR dans la population generale ont augmente au Botswana, en Republique de Coree et au Perou et diminue en Estonie, Lettonie et aux Etats-Unis d'Amerique. Conclusion Les taux mondiaux les plus eleves jamais signales de TBUR ont ete documentes en 2009 et 2010. Les tendances de la TB-UR sont encore peu claires dans la plupart des parametres. De meilleures donnees de surveillance ou d'enquete sont necessaires, surtout en provenance d'Afrique et d'Inde. [TEXT NOT REPRODUCIBLE IN ASCII.] Vigilancia de la resistencia a los medicamentos contra la tuberculosis en todo el mundo: analisis actualizado, 2007-2010 Objetivo Presentar una actualizacion global de la situacion de la tuberculosis (TB) resistente a los medicamentos y analizar las tendencias entre 1994 y 2010. Metodo Se analizaron los datos sobre la resistencia a los medicamentos entre los pacientes recien diagnosticados con TB y los que habian recibido tratamiento con anterioridad, en base a los informes que los paises remitieron a la Organizacion Mundial de la Salud. Dichos datos se recopilaron a traves de encuestas representativas a pacientes o mediante sistemas de vigilancia basados en pruebas rutinarias de sensibilidad a los medicamentos. A traves de una regresion logistica se analizaron las asociaciones existentes entre la tuberculosis multirresistente (TB-MDR), el virus de la inmunodeficiencia humana y el sexo. Resultados Entre 2007 y 2010, 80 paises y 8 territorios facilitaron sus datos de vigilancia. Los niveles mas elevados de TB-MDR entre los casos recien diagnosticados y previamente tratados se registraron en la Federacion de Rusia (Murmansk oblast, 28,9%) y la Republica de Moldova (65,1%), respectivamente. En tres de los paises de la antigua Union Sovietica y en Sudafrica, mas de un 10% de los casos de TB-MDR fueron extremadamente resistentes. Entre 1994 y 2010 se observo en todo el mundo una multirresistencia de un 3,4% (95% de intervalo de confianza, IC: 1,9-5,0) en todos los casos nuevos de TB y de un 19,8% (95% IC: 14,4-25,1) en los casos de TB previamente tratados. No se observaron asociaciones globales entre la TB-MDR y la infeccion por el VIH (cociente de posibilidades, OR: 1,4; IC del 95%: 0,7-3,0) ni con el sexo (OR: 1,1; IC del 95%: 0,8-1,4). Entre los anos 1994 y 2010, las tasas de TB-MDR en la poblacion general aumentaron en Botswana, la Republica de Corea y Peru y descendieron en Estonia, Letonia y Estados Unidos de America. Conclusion En 2009 y 2010 se registraron las tasas globales de MDR-TB mas altas de la historia. Las tendencias de TB-MDR siguen sin quedar claras en la mayoria de los entornos. Es necesaria una mejor vigilancia o mas datos procedentes de encuestas, especialmente en los casos de africa e India., Introduction Surveillance of resistance to drugs against tuberculosis (TB) is a cornerstone of any TB control programme. Surveillance data on drug resistance are needed to track the effectiveness of TB [...]

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 [...]

Abstract Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection.

Abstract Background TB and HIV form a deadly synergy in much of the developing world, especially Africa. Interventions to reduce the impact of these diseases at community level are urgently needed. This paper presents the design of a community randomised trial to evaluate the impact of two complex interventions on the prevalence of tuberculosis (TB) in high HIV prevalence settings in Zambia and South Africa. Methods The interaction between TB and HIV is reviewed and possible interventions that could reduce the prevalence of TB in HIV-endemic populations are discussed. Two of these interventions are described in detail and the design of a 2 × 2 factorial community randomised trial to test these interventions is presented. The limitations and challenges of the design are identified and discussed. Conclusion There is an urgent need to reduce the prevalence of TB in communities highly affected by HIV. Potential interventions are complex and require innovative trial designs to provide the rigorous evidence needed to inform health policy makers and to ensure that resources are used optimally. Trial Registration Number: ISRCTN36729271

Abstract Background In the pre-intervention year of a randomized controlled trial investigating the protective effects of house screening against malaria-transmitting vectors, a multi-factorial risk factor analysis study was used to identify factors that influence mosquito house entry. Methods Mosquitoes were sampled using CDC light traps in 976 houses, each on one night, in Farafenni town and surrounding villages during the malaria-transmission season in The Gambia. Catches from individual houses were both (a) left unadjusted and (b) adjusted relative to the number of mosquitoes caught in four sentinel houses that were operated nightly throughout the period, to allow for night-to-night variation. Houses were characterized by location, architecture, human occupancy and their mosquito control activities, and the number and type of domestic animals within the compound. Results 106,536 mosquitoes were caught, of which 55% were Anopheles gambiae sensu lato, the major malaria vectors in the region. There were seven fold higher numbers of An. gambiae s.l. in the villages (geometric mean per trap night = 43.7, 95% confidence intervals, CIs = 39.5–48.4) than in Farafenni town (6.3, 5.7–7.2) and significant variation between residential blocks (p < 0.001). A negative binomial multivariate model performed equally well using unadjusted or adjusted trap data. Using the unadjusted data the presence of nuisance mosquitoes was reduced if the house was located in the town (odds ratio, OR = 0.11, 95% CIs = 0.09–0.13), the eaves were closed (OR = 0.71, 0.60–0.85), a horse was tethered near the house (OR = 0.77, 0.73–0.82), and churai, a local incense, was burned in the room at night (OR = 0.56, 0.47–0.66). Mosquito numbers increased per additional person in the house (OR = 1.04, 1.02–1.06) or trapping room (OR = 1.19, 1.13–1.25) and when the walls were made of mud blocks compared with concrete (OR = 1.44, 1.10–1.87). Conclusion This study demonstrates that the risk of malaria transmission is greatest in rural areas, where large numbers of people sleep in houses made of mud blocks, where the eaves are open, horses are not tethered nearby and where churai is not burnt at night. These factors need to be considered in the design and analysis of intervention studies designed to reduce malaria transmission in The Gambia and other parts of sub-Saharan Africa.

Abstract Background Type 2 diabetes is an important cause of morbidity and mortality. Its prevalence appears to be increasing. Guidelines exist regarding its management. Recommendations regarding drug therapy have changed. Little is known about the influence of these guidelines and changed recommendations on the actual management of patients with type 2 diabetes. This study aims to document trends in the prevalence, drug treatment and recording of measures related to the management of type 2 diabetes; and to assess whether recommended targets can be met. Methods The population comprised subjects registered between 1994 and 2001 with 74 general practices in England and Wales which routinely contribute to the Doctors' Independent Network database. Approximately 500,000 patients and 10,000 type 2 diabetics were registered in each year. Results Type 2 diabetes prevalence rose from 17/1000 in 1994 to 25/1000 in 2001. Drug therapy has changed: use of long acting sulphonylureas is falling while that of short acting sulphonylureas, metformin and newer therapies including glitazones is increasing. Electronic recording of HbA1c, blood pressure, cholesterol and weight have risen steadily, and improvements in control of blood pressure and cholesterol levels have occurred. However, glycaemic control has not improved, and obesity has increased. The percentage with a BMI under 25 kg/m2 fell from 27.0% in 1994 to 19.4% in 2001 (p < 0.001). Conclusion Prevalence of type 2 diabetes is increasing. Its primary care management has changed in accordance with best evidence. Monitoring has improved, but further improvement is possible. Despite this, glycaemic control has not improved, while the prevalence of obesity in the diabetic population is rising.

Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1) and the leading cause of death among persons living with human immunodeficiency virus (HIV) infection, accounting for approximately 40% of deaths in this population (2). The United Nations' (UN) Sustainable Development Goals (3) and the World Health Organization's (WHO's) End TB Strategy (4) have defined ambitious targets for 2020-2035, including a 35% reduction in the absolute number of TB deaths and a 20% reduction in TB incidence by 2020, compared with 2015 (4). Since 2000, WHO has produced annual TB estimates for all countries (1). Global and regional disease estimates were evaluated for 2017 to determine progress toward meeting targets. In 2017, an estimated 10 million incident cases of TB and 1.57 million TB deaths occurred, representing 1.8% and 3.9% declines, respectively, from 2016. Numbers of TB cases and disease incidence were highest in the WHO South-East Asia and Africa regions, and 9% of cases occurred among persons with HIV infection. Rifampicin-resistant (RR) or multidrug-resistant (MDR) (resistance to at least both isoniazid and rifampicin) TB occurred among 3.6% and 18% of new and previously treated TB cases, respectively (5.6% among all cases). Overall progress in global TB elimination was modest in 2017, consistent with that in recent years (1); intensified efforts to improve TB diagnosis, treatment, and prevention are required to meet global targets for 2020-2035. [ABSTRACT FROM AUTHOR]