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: Objective: This study aimed to assess the feasibility of conducting a representative tuberculin skin test (TST) survey for M?ori in Aotearoa New Zealand and to estimate the prevalence of latent tuberculosis (TB) infection. Methods: Participants were M?ori in the Waikato region, recruited by a M?ori nurse, through: 1) random household selection from the Electoral Roll; 2) randomly selected prison inmates; and 3) community and health settings. A TB history and symptoms questionnaire was completed, TST performed and investigation of those with TST induration ?10mm. Results: Random household selection was resource intensive and only contributed 14 participants. Repeated random selection of prison lists were required to recruit 207 participants and there were no positive TST cases. Community and health settings yielded the highest participation (n=370) and the three people (0.5%) with TST ?10mm. Age ?45 years and history of contact with a TB case were associated with TST induration ?5mm (n=39; 6.6%). Conclusions: The community and health settings were the only feasible options for recruitment. The overall prevalence of a positive TST in the study population was low. A 5mm cut?off may be best to maximise sensitivity for future studies. Implications for public health: A mixture of sample selection processes that are more targeted are needed to identify M?ori with latent TB infection., The World Health Assembly in May 2014 approved a new Global Tuberculosis (TB) Strategy with ambitious goals.[sup.1] The Strategy aimed to end the global TB epidemic, with targets to reduce [...]

BackgroundTens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood.MethodsIn this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protocol is registered with PROSPERO (CRD42018087022).FindingsIn total, study groups from 46 cohort studies in 34 countries-29 (63%) prospective studies and 17 (37%) retrospective-agreed to share their data and were included in the final analysis. 137 647 tuberculosis-exposed children were evaluated at baseline and 130 512 children were followed for 429 538 person-years, during which 1299 prevalent and 999 incident tuberculosis cases were diagnosed. Children not receiving preventive therapy with a positive result for tuberculosis infection had significantly higher 2-year cumulative tuberculosis incidence than children with a negative result for tuberculosis infection, and this incidence was greatest among children below 5 years of age (19·0% [95% CI 8·4-37·4]). The effectiveness of preventive therapy was 63% (adjusted HR 0·37 [95% CI 0·30-0·47]) among all exposed children, and 91% (adjusted HR 0·09 [0·05-0·15]) among those with a positive result for tuberculosis infection. Among all children

Meningitis is a relatively rare form of tuberculosis, but it carries a high mortality rate, reaching 50% in some settings, with higher rates among patients with HIV co-infection and those with drug-resistant disease. Most studies of tuberculosis meningitis (TBM) tend to focus on better diagnosis, drug treatment and supportive care for patients in hospital. However, there is significant variability in mortality between settings, which may be due to specific variation in the availability and quality of health care services, both prior to, during, and after hospitalization. Such variations have not been studied thoroughly, and we therefore present a theoretical framework that may help to identify where efforts should be focused in providing optimal services for TBM patients. As a first step, we propose an adjusted cascade of care for TBM and patient pathway studies that might help identify factors that account for losses and delays across the cascade. Many of the possible gaps in the TBM cascade are related to health systems factors; we have selected nine domains and provide relevant examples of systems factors for TBM for each of these domains that could be the basis for a health needs assessment to address such gaps. Finally, we suggest some immediate action that could be taken to help make improvements in services. Our theoretical framework will hopefully lead to more health system research and improved care for patients suffering from this most dangerous form of tuberculosis.

In Fiji, the SARS-CoV-2 Delta variant wave occurred in a largely unvaccinated and nonimmune population during April-November 2021 (1). A risk-based COVID-19 vaccine rollout strategy commenced in March 2021, and, [...]

Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Tuberculosis (TB) is the infectious disease that causes the most deaths worldwide ([approximately equal to] 5,000/day) (1). Of major concern is the increasing prevalence of drug resistance worldwide (1). There [...]

Vaccine development against tuberculosis (TB) is based on the induction of adaptive immune responses endowed with long-term memory against mycobacterial antigens. Memory B and T cells initiate a rapid and robust immune response upon encounter with Mycobacterium tuberculosis, thus achieving long-lasting protection against infection. Recent studies have shown, however, that innate immune cell populations such as myeloid cells and NK cells also undergo functional adaptation after infection or vaccination, a de facto innate immune memory that is also termed trained immunity. Experimental and epidemiological data have shown that induction of trained immunity contributes to the beneficial heterologous effects of vaccines such as bacille Calmette-Guerin (BCG), the licensed TB vaccine. Moreover, increasing evidence argues that trained immunity also contributes to the anti-TB effects of BCG vaccination. An interaction among immunological signals, metabolic rewiring, and epigenetic reprogramming underlies the molecular mechanisms mediating trained immunity in myeloid cells and their bone marrow progenitors. Future studies are warranted to explore the untapped potential of trained immunity to develop a future generation of TB vaccines that would combine innate and adaptive immune memory induction., Introduction Vaccination has made an enormous contribution to improving human and animal health over the last two centuries (1-6). Despite progress in developing vaccines against a large number of infections, [...]

In 2016, invasive bacterial diseases accounted for one quarter of the 5.6 million childhood deaths worldwide (1). Most invasive bacterial diseases occur in sub-Saharan Africa and other low- and middle-income [...]

BackgroundHelicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis.Methodology/principal findingsWe first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04).Conclusions/significanceH. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Objective To evaluate the performance of diagnostic tools for diabetes mellitus, Including laboratory methods and clinical risk scores, In newly-diagnosed pulmonary tuberculosis patients from four middle-income countries.Methods In a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania ' and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen Initial random plasma glucose was [greater than or equal to] 6.1 mmol/L.Findings The overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6-14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75-0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81-0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru.Conclusion Random plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemla, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation.Objectif Evaluer la performance des outils de diagnostic du diabete sucre, et notamment les methodes de laboratoire et les cotes de risque clinique, chez les patients souffrant d'une tuberculose pulmonaire recemment diagnostiquee dans quatre pays a revenu intermediaire.Methodes Dans le cadre d'une etude multicentrique et prospective, nous avons recrute 2185 patients atteints de tuberculose pulmonaire dans differents endroits en Afrique du Sud, en Indonesie, au Perou et en Roumanie entre janvier 2014 et septembre 2016. En utilisant comme referencel'hemoglobineglyquee (HbA1c) mesuree en laboratoire, nous avons evalue la precision diagnostique de la glycemie aleatoire, de l'HbAI c sur le lieu d'intervention, de la glycemie a jeun, de la bandelette urinaire, des cotes de risque deja publiees et recemment obtenues pour le diabete sucre et des mesures anthropometriques. Nous avons egalement analyse des combinaisons de tests, et notamment un test en deux etapes qui utilise l'HbA1c sur le lieu d'intervention lorsque la glycemie aleatoire initiale est [greater than or equal to] 6,1 mmol/LResultats La prevalence brute generale du diabete sucre chez les patients souffrant d'une tuberculose recemment diagnostiquee etait de 283/2185 (13,0%; intervalle de confiance, IC, a 95%: 11,6-14,4). Le marqueur fournissant la meilleure precision diagnostique etait l'HbA1c sur le lieu d'intervention (aire sous la courbe ROC: 0,81; IC a 95%: 0,75-0,86). La meilleure precision diagnostique generale a ete obtenue a l'aide d'une cote de risque calculee au moyen de l'age, de l'HbA1c sur le lieu d'intervention et de la glycemie aleatoire (aire sous la courbe ROC: 0,85; IC a 95%: 0,81-0,90). Une forte heterogeneite entre les differents endrolts a ete constatee pourtous les marqueurs, mais le test en deux etapes a donne de bons resultats en Indonesie et au Perou.Conclusion L'utilisation de la glycemie aleatoire suivie de l'HbA1c sur le lieu d'intervention permet de diagnostiquer avec precision le diabete chez les patients atteints de tuberculose, en particulier lorsqu'ils souffrent d'une importante hyperglycemie, tout en diminuant le besoin de tests HbA1c sur le lieu d'intervention, plus couteux. Les cotes de risque associees ou non a des donnees biochimiques peuvent etre utiles, mais doivent etre validees.Objetivo Evaluar el rendimiento de las herramientas de diagnostico para la diabetes mellitus, incluidos los metodos de laboratorio y los indices de riesgo clinico, en pacientes recien diagnosticados con tuberculosis pulmonar de cuatro paises de ingresos medios.Metodos En un estudio prospectivo multicentrico, se seleccionaron 2185 pacientes con tuberculosis pulmonar de algunas regiones de Indonesia, Peru, Rumania y Sudafrica entre enero de 2014 y septiembre de 2016. Usando hemoglobina glicosilada medida en laboratorio (HbA1 c) como el patron de excelencia, se midio la precision diagnostica de glucosa plasmatica al azar, estando HbA1 c en el punto de atencion, glucemia en sangre en ayunas, tira reactiva de orina, indices de riesgo de diabetes mellitus publicados recientemente y medidas antropometricas. Tambien se analizaron combinaciones de pruebas, incluida una prueba de dos pasos con HbA1c en el punto de atencion cuando la glucosa plasmatica aleatoria inicial fue [greater than or equal to] 6,1 mmol/L.Resultados La prevalencia general cruda de diabetes mellitus entre los pacientes con tuberculosis recien diagnosticados fue de 283/2185 (13,0 %, intervalo de confianza del 95 %, IC: 11,6-14,4). El marcador con la mejor precision diagnostica fue la HbA1c en el punto de atencion (area bajo la curva caracteristica operativa del receptor: 0,81; IC del 95 %: 0,75-0,86). Un indice de riesgo derivado de la edad, la HbA1c en el punto de atencion y la glucosa plasmatica al azar obtuvieron la mejor precision diagnostica general (area bajo la curva: 0,85; IC del 95 %: 0,81 -0,90). Hubo una heterogeneidad sustancial entre las regiones para todos los marcadores, pero la prueba combinada de dos pasos funciono de manera correcta en Indonesia y Peru.Conclusion La glucosa plasmatica al azar seguida de la prueba de HbA1c en el punto de atencion puede diagnosticar con precision la diabetes en pacientes con tuberculosis, particularmente en aquellos con hiperglucemia sustancial, mientras se reduce la necesidad de pruebas mas costosas de HbA1 c en el punto de atencion. Los indices de riesgo con o sin datos bioquimicos pueden ser utiles, pero requieren validacion., [phrase omitted]IntroductionTuberculosis is a major global public health concern. In 2016, the World Health Organization (WHO) estimated that there were 10.4 million new tuberculosis patients worldwide and 1.8 million tuberculosis-related [...]