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BackgroundThe World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L-1 cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs).MethodsFollowing a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal-external cross-validation to evaluate performance.ResultsWe pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg·L-1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg·L-1 cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively.ConclusionsCRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L-1 cut-off or in a CPM depends on available resources.

BackgroundThe WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.MethodsIn this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.FindingsWe identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (

Objective: To investigate the prevalence of non‐communicable diseases among household contacts of people with tuberculosis. Methods: We conducted a systematic review and individual participant data meta‐analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non‐communicable disease among household contacts of people with clinical tuberculosis. We estimated the non‐communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta‐analyses. Furthermore, we compared age and sex‐standardised non‐communicable disease prevalence with national‐level estimates standardised for age and sex. Results: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta‐analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%–14.9%, four studies). Age‐and sex‐standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self‐report or medical records was 3.4% (95% CI 2.6%–4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta‐analysis. There were limited data for other non‐communicable diseases. Conclusion: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non‐communicable diseases and address shared risk factors. [ABSTRACT FROM AUTHOR]

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 develop and test a simple system for recording and reporting the diagnosis and treatment of latent tuberculosis infection and to compare the effects of passive and active tracing of child contacts on indicators of such infection. Methods We revised Burkina Faso's latent tuberculosis infection register and quarterly tuberculosis reporting form. Subsequently, coverage of the routine screening of contacts, who were younger than five years, for active tuberculosis and the corresponding percentages of such contacts who, if eligible, initiated preventive therapy were measured, nationwide, between 1 April 2016 and 31 March 2017. In 2016, we evaluated indicators of latent tuberculosis infection in the Hauts-Bassins region before and after community health workers had begun the active tracing of contacts who were younger than five years. Findings In Burkina Faso, during our study period, 3717 cases of pulmonary tuberculosis and 1166 corresponding contacts who were younger than five years were reported as the result of routine screening and passive contact tracing. The overall contact: index ratio was 0.31 and corresponding screening coverage was 82.0% (956/1166) and proportion of children starting on preventive treatment was 90.5% (852/941). Active tracing in Hauts-Bassins led to a substantially higher contact/index ratio (1.83) and screening coverage (99.3%; 145/146). Conclusion The newly established recording and reporting system proved feasible and user-friendly and allowed measurement of global indicators of latent tuberculosis infection. Compared with active tracing, passive tracing led to much lower estimates of the numbers of child contacts. Objectif Elaborer et testerun systeme simple pour enregistrer et declarer le diagnostic et le traitement des cas d'infection tuberculeuse latente et comparer les effets de la recherche passive et active des contacts enfants sur les indicateurs de cette infection. Methodes Nous avons passe en revue le registre des infections tuberculeuses latentes et le formulaire de rapport trimestriel des cas de tuberculose du Burkina Faso. Ensuite, nous avons mesure, dans tout le pays, entre le 1er avril 2016 et le 31 mars 2017, le taux de couverture du depistage systematique de la tuberculose active chez les contacts ages de moins de cinq ans et les pourcentages correspondants de contacts qui, s'ils remplissaient les conditions requises, avaient commence un traitement preventif. En 2016, nous avons evalue les indicateurs de l'infection tuberculeuse latente dans la region des Hauts-Bassins avant et apres que les agents de sante communautaires ont commence la recherche active des contacts ages de moins de cinq ans. Resultats Au Burkina Faso, au cours de la periode etudiee, 3717 cas de tuberculose pulmonaire et 1166 contacts correspondants ages de moins de cinq ans ont ete declares dans le cadre du depistage systematique et de la recherche passive des contacts. Le ratio total contacts/cas index etait de 0,31 et le taux de couverture du depistage correspondant s'elevait a 82,0% (956/1166), tandis que la proportion d'enfants ayant commence un traitement preventif etait de 90,5% (852/941). La recherche active dans les Hauts-Bassins a entraine une hausse sensible du ratio total contacts/cas index (1,83) et du taux de couverture du depistage (99,3%; 145/146). Conclusion Le nouveau systeme d'enregistrement et de declaration s'est avere utilisable et convivial et a permis de mesurer les indicateurs globaux de l'infection tuberculeuse latente. En comparaison avec la recherche active, la recherche passive a genere des estimations beaucoup plus faibles du nombre de contacts enfants. Objetivo Desarrollar y probar un sistema simple de registro y presentacion de informes sobre el diagnostico y el tratamiento de la infeccion tuberculosa latente y comparar los efectos del seguimiento pasivo y activo de los contactos infantiles con indicadores de dicha infeccion. Metodos Se reviso el registro de infeccion tuberculosa latente de Burkina Faso y el formulario trimestral de informacion sobre la tuberculosis. Posteriormente, se midio la cobertura de los examenes de deteccion rutinarios a los contactos, menores de cinco anos, para la tuberculosis activa y los porcentajes correspondientes de contactos que, de ser aptos, iniciaron la terapia preventiva a nivel nacional, entre el 1 de abril de 2016 y el 31 de marzo de 2017. En 2016, se evaluaron los indicadores de infeccion tuberculosa latente en la region de Hauts-Bassins antes y despues de que los trabajadores comunitarios de la salud empezaran el seguimiento activo de los contactos menores de cinco anos. Resultados En Burkina Faso, en nuestro periodo de estudio, se registraron 3717 casos de tuberculosis pulmonar y 1166 contactos correspondientes de menos de cinco anos como resultado de un examen rutinario y un seguimiento del contacto pasivo. La tasa global de indice de contacto fue del 0,31 y la cobertura de deteccion correspondiente fue del 82,0% (956/1166), ademas, la proporcion de ninos que iniciaron el tratamiento preventivo fue del 90,5% (852/941). El seguimiento activo en Hauts-Bassins dio lugar a una relacion de contacto/indice (1,83) y una cobertura de deteccion (99,3%; 145/146) sustancialmente mas altas. Conclusion El recien establecido sistema simple de registro y presentacion de informes resulto factible y facil de usar y permitio la medicion de indicadores globales de la infeccion tuberculosa latente. En comparacion con el seguimiento activo, el seguimiento pasivo dio lugar a estimaciones mucho mas bajas de la cantidad de contactos secundarios., Introduction The identification and treatment of individuals with latent Mycobacterium tuberculosis infection is an essential element of the World Health Organizations (WHO's) End TB Strategy. (1) Individuals with such infection, [...]

Objective To review policies on management of latent tuberculosis infection in countries with low and high burdens of tuberculosis. Methods We divided countries reporting data to the World Health Organization (WHO) Global Tuberculosis Programme into low and high tuberculosis burden, based on WHO criteria. We identified national policy documents on management of latent tuberculosis through online searches, government websites, WHO country offices and personal communication with programme managers. We made a descriptive analysis with a focus on policy gaps and deviations from WHO policy recommendations. Findings We obtained documents from 68 of 113 low-burden countries and 30 of 35 countries with the highest burdens of tuberculosis or human immunodeficiency virus (HIV)-associated tuberculosis. Screening and treatment of latent tuberculosis infection in people living with HIV was recommended in guidelines of 29 (96.7%) high-burden and 54 (79.7%) low-burden countries. Screening for children aged < 5 years with household tuberculosis contact was the policy of 25 (83.3%) high- and 28 (41.2%) low-burden countries. In most high-burden countries the recommendation was symptom screening alone before treatment, whereas in all low-burden countries it was testing before treatment. Some low-burden countries' policies did not comply with WHO recommendations: nine (13.2%) recommended tuberculosis preventive treatment for travellers to high-burden countries and 10 (14.7%) for patients undergoing abdominal surgery. Conclusion Lack of solid evidence on certain aspects of management of latent tuberculosis infection results in national policies which vary considerably. This highlights a need to advance research and develop clear, implementable and evidence-based WHO policies. Objectif Passer en revue les politiques relatives a la prise en charge de l'infection tuberculeuse latente de pays faiblement ou fortement touches par la tuberculose. Methodes Nous avons separe les pays qui transmettent des donnees au Programme mondial de lutte contre la tuberculose de l'Organisation mondiale de la Sante (OMS) selon qu'ils presentaient une charge de morbidite tuberculeuse faible ou elevee, suivant les criteres de l'OMS. Nous avons trouve les politiques nationales pour la prise en charge de la tuberculose latente grace a des recherches en ligne, aux sites Internet des gouvernements, aux bureaux de l'OMS dans les pays et a des communications personnelles avec des responsables de programmes. Nous avons fait une analyse descriptive axee particulierement sur les lacunes des politiques et leurs ecarts des recommandations de l'OMS. Resultats Nous avons obtenu des documents de 68 pays sur 113 ayant une faible charge de morbidite tuberculeuse et de 30 pays sur 35 ayant les plus fortes charges de morbidite dues a la tuberculose ou a la tuberculose associee au virus de l'immunodeficience humaine (VIH). Le depistage et le traitement de l'infection tuberculeuse latente chez les personnes vivant avec le VIH etaient recommandes dans les directives de 29 pays (96,7%) a la charge de morbidite elevee et de 54 pays (79,7%) oU cette charge etait faible. Le depistage des enfants de moins de5 ans en contact familial avec la tuberculose etait prevu dans 25 pays (83,3%) a la charge de morbidite elevee et dans 28 (41,2%) a la charge de morbidite faible. Dans la plupart des pays a la charge de morbidite elevee, seule la recherche des symptomes avant traitement etait recommandee, tandis que tous les pays a la charge de morbidite faible recommandaient un depistage avant traitement. Les politiques de certains pays a la charge de morbidite faible ne suivaient pas les recommandations de l'OMS: neuf (13,2%) recommandaient un traitement preventif contre la tuberculose pour les personnes se rendant dans des pays a la charge de morbidite elevee et 10 (14,7%) pour les patients subissant une chirurgie abdominale. Conclusion En l'absence de preuves solides concernant certains aspects de la prise en charge de l'infection tuberculeuse latente, les politiques nationales varient considerablement les unes des autres. Cela met en lumiere la necessite de faire progresser la recherche et, pour l'OMS, d'elaborer des politiques claires, applicables et fondees sur des elements probants. Objetivo Analizar las politicas sobre el tratamiento de la infeccion de tuberculosis latente en paises con niveles bajos y elevados de tuberculosis. Metodos Dividimos a los paises que informan datos al Programa Global de Tuberculosis de la Organizacion Mundial de la Salud (OMS) en nivel de tuberculosis bajo y elevado, conforme a los criterios de la OMS. Identificamos los documentos de politicas nacionales sobre el tratamiento de la tuberculosis latente a traves de busquedas en linea, sitios web gubernamentales, sedes nacionales de la OMS y comunicacion personal con los administradores del programa. Realizamos un analisis descriptivo enfocado en las desviaciones y los vacios de las politicas con respecto a las recomendaciones de politicas de la OMS. Resultados Obtuvimos documentos de 68 de 113 paises con nivel bajo y de 30 de 35 paises con los niveles mas elevados de tuberculosis o tuberculosis asociada con el virus de la inmunodeficiencia humana (VIH). En las pautas de 29 (96,7%) paises con nivel elevado y 54 (79,7%) paises con nivel bajo se recomendaron examenes de deteccion y tratamiento de la Infeccion de tuberculosis latente en personas que viven con el VIH. La politica de 25 (83,3%) paises con nivel elevado y de 28 (41,2%) paises con nivel bajo se baso en examenes de deteccion en ninos menores de cinco anos de edad con contacto domestico con tuberculosis. En casi todos los paises con nivel elevado, la recomendacion consistio unicamente en el examen de deteccion de los sintomas antes del tratamiento, mientras que, en todos los paises con nivel bajo, esta consistio en pruebas antes del tratamiento. Las politicas de algunos paises con nivel bajo no cumplen con las recomendaciones de la OMS: nueve (13,2%) recomendaron el tratamiento preventivo de la tuberculosis para viajeros que se dirijan a paises con nivel elevado y 10 (14,7%) para pacientes que se sometan a una cirugia abdominal. Conclusion La falta de pruebas solidas sobre ciertos aspectos del tratamiento de la infeccion de tuberculosis latente da lugar a politicas nacionales que varian considerablemente. Esto subraya la necesidad de realizar investigaciones avanzadas y desarrollar politicas de la OMS que sean claras, implementables y empiricas. [phrase omitted], Introduction Tuberculosis is currently the leading infectious cause of death worldwide. The World Health Organization (WHO) End Tuberculosis strategy aims to substantially reduce tuberculosis incidence by 90% and mortality by [...]

Background A systematic review showed that the accuracy of Mycobacterium tuberculosis antigen–based skin tests (TBSTs) for tuberculosis is similar to that of interferon γ release assay, but the safety of TBSTs has not been systematically reviewed. Methods We searched for studies reporting injection site reactions (ISRs) and systemic adverse events associated with TBSTs. We searched Medline, Embase, e-library, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure database for studies through 30 July 2021, and the database search was updated until 22 November 2022. Results We identified 7 studies for Cy-Tb (Serum Institute of India), 7 (including 2 found through the updated search) for C-TST (Anhui Zhifei Longcom), and 11 for Diaskintest (Generium). The pooled risk of any injection site reactions (ISRs) due to Cy-Tb (n = 2931; 5 studies) did not differ significantly from that for tuberculin skin tests (TSTs; risk ratio, 1.05 [95% confidence interval,.70–1.58]). More than 95% of ISRs were reported as mild or moderate; common ISRs included pain, itching, and rash. In 1 randomized controlled study, 49 of 153 participants (37.6%) given Cy-Tb experience any systemic adverse event (eg, fever and headache), compared with 56 of 149 participants (37.6%) given TST (risk ratio, 0.85 [95% confidence interval,.6–1.2]). In a randomized controlled study in China (n = 14 579), the frequency of systemic adverse events in participants given C-TST was similar to that for TST, and the frequency of ISRs was similar to or lower than that for TST. Reporting of the safety data on Diaskintest was not standardized, precluding meta-analysis. Conclusion The safety profile of TBSTs appears similar to that of TSTs and is associated with mostly mild ISRs. [ABSTRACT FROM AUTHOR]

Reports suggest an increased risk of tuberculosis (TB) in people with chronic airway diseases (CADs) such as chronic obstructive pulmonary disease (COPD), but evidence has not been systematically reviewed. We performed a systematic review by searching MEDLINE and Embase for studies published from 1 January 1993 to 15 January 2021 reporting the association between the incident risk of TB in people with CADs (asthma, COPD and bronchiectasis). Two reviewers independently assessed the quality of individual studies. We included nine studies, with two from low-income high TB burden countries. Three cohort studies reported a statistically significant independent association between COPD and the risk of TB in high-income countries (n=711 389). Hazard ratios for incident TB ranged from 1.44 to 3.14 adjusted for multiple confounders including age, sex and comorbidity. There was large between-study heterogeneity (I2=97.0%) across studies. The direction of effect on the TB risk from asthma was inconsistent. Chronic bronchitis or bronchiectasis studies were limited. The small number of available studies demonstrated an increased risk of TB in people with COPD; however, the magnitude of the increase varies by setting and population. Data in high TB burden countries and for other CADs are limited. [ABSTRACT FROM AUTHOR]