Curving Tuberculosis: Current Trends and Future Needs

Tuberculosis (TB) presents new challenges as a global public health problem, especially at a time of increasing threats to some particular patients due to Human Immunodeficiency Virus (HIV) infection and multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The World Health Assembly strives to reduce TB deaths by 95% and to decrease TB incidence by 95% by 2035. However, new approaches are necessary in order to attain these objectives. Such approaches include active ascertainment of cases in high risk populations, increasing the availability of accurate point-of-care testing, rapid detection of drug resistance, novel vaccines, and new prophylaxis and treatment regimens (particularly for MDR and XDR TB). The ultimate objective of those programs is to develop highly effective drug regimens that can achieve high cure rates regardless of strains’ resistance patterns

Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment

Ajuda rebuda: Sociedad Española de Pneumología y Cirugía Torácica (207/2011)Objective: To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. Methods: TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8-283.4); being retired (HR = 2.4;CI:1.1-5.1); having visited the emergency department (HR = 3.1;CI:1.2-7.7); HIV infection (HR = 3.4;CI:1.6-7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2-3.3) or non-standard treatments (HR = 2.68;CI:1.36-5.25); comprehension difficulties (HR = 2.8;CI:1.3-6.1); and smear-positive sputum (HR = 2.3-CI:1.0-4.8). Conclusion: There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs

Social, Clinical and Microbiological Differential Characteristics of Tuberculosis among Immigrants in Spain

BACKGROUND: To identify the differential tuberculosis (TB) characteristics within the immigrant population with respect to natives in Spain. METHODOLOGY/PRINCIPAL FINDINGS: A prospective cohort study design was implemented to examine the TB cases diagnosed and starting standard antituberculous treatment in Spain, between January 1st 2006 and March 31st 2007. A logistic regression analysis was performed to determine differential characteristics. 1,490 patients were included in the study population, 1,048 natives and 442 (29.7%) immigrants. According to the multivariate analysis, the following variables were significantly associated with immigrant TB cases: younger age (OR = 3.79; CI:2.16-6.62), living in group situation (OR = 7.61; CI:3.38-12.12), lower frequency of disabled (OR:0.08; CI:0.02-0.26) and retired (OR:0.21; CI:0.09-0.48) employment status, lower frequency of pulmonary disease presentation (OR = 0.47; CI:0.24-0.92), primary or emergency care admission (OR = 1.80; CI:1.05-3.06 and OR = 2.16; CI:1.36-3.45), drug resistance (OR = 1.86; CI:1.01-3.46), treatment default (OR:2.12; CI:1.18-3.81), lower frequency of alcohol and cigarette consumption (OR = 2.10; CI:1.42-3.11 and OR = 2.85; CI:2.10-3.87 respectively), more directly observed treatment (OR = 1.68; CI:1.04-2.69), and poor understanding of TB disease and its treatment (OR = 3.11; CI:1.86-5.20). The low percentage of primary MDR-TB in the native population (0.1% vs. 2.2% of immigrants) should be noted. CONCLUSIONS/SIGNIFICANCE: The differences show the need to introduce specific strategies in the management of TB within the immigrant population, including the improvement of social and work conditions

Albino T-DNA tomato mutant reveals a key function of 1-deoxy-D-xylulose-5-phosphate synthase (DXS1) in plant development and survival

[EN] Photosynthetic activity is indispensable for plant growth and survival and it depends on the synthesis of plastidial isoprenoids as chlorophylls and carotenoids. In the non-mevalonate pathway (MEP), the 1-deoxy-D-xylulose-5-phosphate synthase 1 (DXS1) enzyme has been postulated to catalyze the ratelimiting step in the formation of plastidial isoprenoids. In tomato, the function of DXS1 has only been studied in fruits, and hence its functional relevance during plant development remains unknown. Here we report the characterization of the wls-2297 tomato mutant, whose severe deficiency in chlorophylls and carotenoids promotes an albino phenotype. Additionally, growth of mutant seedlings was arrested without developing vegetative organs, which resulted in premature lethality. Gene cloning and silencing experiments revealed that the phenotype of wls-2297 mutant was caused by 38.6 kb-deletion promoted by a single T-DNA insertion affecting the DXS1 gene. This was corroborated by in vivo and molecular complementation assays, which allowed the rescue of mutant phenotype. Further characterization of tomato plants overexpressing DXS1 and comparative expression analysis indicate that DXS1 may play other important roles besides to that proposed during fruit carotenoid biosynthesis. Taken together, these results demonstrate that DXS1 is essentially required for the development and survival of tomato plants.This work was supported by research grants from the Spanish Ministry of Economy and Competitiveness and the UE-European Regional Development Fund (AGL2015-64991-C3-1-R, and AGL2015-64991-C3-3-R), and Junta de Andalucia (P12-AGR-1482). PhD fellowship to M.G.-A. was funded by the FPU Programme of the Spanish Ministry of Science and Innovation. The authors thank research facilities provided by the Campus de Excelencia Internacional Agroalimentario (CeiA3).Garcia-Alcazar, M.; Giménez Caminero, ME.; Pineda Chaza, BJ.; Capel, C.; García Sogo, B.; Sánchez Martín-Sauceda, S.; Yuste-Lisbona, FJ.... (2017). Albino T-DNA tomato mutant reveals a key function of 1-deoxy-D-xylulose-5-phosphate synthase (DXS1) in plant development and survival. Scientific Reports. 7:1-12. https://doi.org/10.1038/srep45333112

Co-infection with Pansensitive and Multidrug-Resistant Strains of Mycobacterium tuberculosis

We report a case of a 23-year-old HIV-negative man with multidrug-resistant Mycobacterium tuberculosis that became evident while he was being treated for M. tuberculosis that was sensitive to all first-line drugs. This case should alert clinicians to consider co-infection as a possible cause of recrudescent disease

Paleofitogeografía de los pinares en las montañas periféricas de la cuenca del Duero

En las dos últimas décadas se han obtenido numerosos resultados procedentes de diferentes trabajos paleobotánicos (Cuaternario final) realizados en los territorios montanos periféricos de la depresión del Duero. Las metodologías empleadas han sido diversas y tienen que ver con los diferentes tipos de yacimientos y de muestras biológicas seleccionadas para su estudio; entre ellas destacan las técnicas de microscopía óptica para la identificación de maderas subfósiles, la morfología comparada de macrorrestos y los estudios dendrocronológicos en árboles longevos y maderas subfósiles. En esta comunicación se reúnen y resumen los trabajos más importantes, haciéndose una síntesis de las conclusiones obtenidas en los trabajos paleofitogeográficos realizados hasta el momento; se hace hincapié en la información proporcionada por los macrorrestos (maderas, estróbilos) así como por la recogida en los registros dendrocronológicos (con extensión a la dendroecología). Otro de los objetivos de la comunicación es la síntesis de las conclusiones obtenidas en los trabajos paleofitogeográficos realizados hasta el momento. Uno de esos resultados es que el comportamiento de los pinares a lo largo del Holoceno presenta diferentes modalidades en cada una de las cordilleras que bordean la cuenca del Duero; desde casos con marcada estabilidad a otros en que se muestran variaciones temporales apreciables (con patrones de heterogeneidad en función de un eje N-S y/o O-E

Multidrug-resistant Tuberculosis Management in Resource-limited Settings

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings

High use of private providers for first healthcare seeking by drug-resistant tuberculosis patients: a cross-sectional study in Yangon, Myanmar.

BACKGROUND: Drug resistance is a growing challenge to tuberculosis (TB) control worldwide, but particularly salient to countries such as Myanmar, where the health system is fragmented across the public and private sector. A recent systematic review has identified a critical lack of evidence for local policymaking, particularly in relation to drivers of drug-resistance that could be the target of preventative efforts. To address this gap from a health systems perspective, our study investigates the healthcare-seeking behavior and preferences of recently diagnosed patients with drug-resistant tuberculosis (DR-TB), focusing on the use of private versus public healthcare providers. METHODS: The study was conducted in ten townships across Yangon with high DR-TB burden. Patients newly-diagnosed with DR-TB by GeneXpert were enrolled, and data on healthcare-seeking behavior and socio-economic characteristics were collected from patient records and interviews. A descriptive analysis of healthcare-seeking behavior was followed by the investigation of relationships between socio-economic factors and type of provider visited upon first feeling unwell, through univariate logistic regressions. RESULTS: Of 202 participants, only 8% reported first seeking care at public facilities, while 88% reported seeking care at private facilities upon first feeling unwell. Participants aged 25-34 (Odds Ratio = 0.33 [0.12-0.95]) and males (Odds Ratio = 0.39 [0.20-0.75]) were less likely to visit a private clinic or hospital than those aged 18-24 and females, respectively. In contrast, participants with higher income were more likely to utilize private providers. Prior to DR-TB diagnosis, 86% of participants took medications from private providers. After DR-TB diagnosis, only 7% of participants continued to take medications from private providers. CONCLUSION: In urban Myanmar, most patients shifted to being managed exclusively in the public sector after being formally diagnosed with DR-TB. However, since the vast majority of DR-TB patients first visited private providers in the period leading to diagnosis, related issues such as unregulated quality of care, potential delays to diagnosis, and lack of care continuity may greatly influence the emergence of drug-resistance. A greater understanding of the health system and these healthcare-seeking behaviors may simultaneously strengthen TB control programmes and reduce government and out-of-pocket expenditures on the management of DR-TB

Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda

Frank Cobelens and colleagues outline key research questions that need to be addressed to maximize the impact of programmatic management of drug-resistant tuberculosis