Genetic differences between different Mycobacterium tuberculosis complex (MTBC) strains determine their ability to transmit within different host populations, their latency times, and their drug ...resistance profiles. Said differences usually emerge through de novo mutations and are maintained or discarded by the balance of evolutionary forces. Using a dataset of ∼5,000 strains representing global MTBC diversity, we determined the past and present selective forces that have shaped the current variability observed in the pathogen population. We identified regions that have evolved under changing types of selection since the time of the MTBC common ancestor. Our approach highlighted striking differences in the genome regions relevant for host–pathogen interaction and, in particular, suggested an adaptive role for the sensor protein of two-component systems. In addition, we applied our approach to successfully identify potential determinants of resistance to drugs administered as second-line tuberculosis treatments.
In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based ...antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting.
In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay.
WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8-94·4) for isoniazid, 73·3% (44·9-92·2) for rifampicin, 50·0% (21·1-78·9) for ethambutol, and 57·1% (34·0-78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected.
We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting.
European Research Council and the Spanish Ministerio de Ciencia.
Tuberculosis resistance diagnostics have vastly improved in recent years thanks to the development of standardised phenotypic and molecular testing methods. However, these methods are either slow or ...limited in the number of resistant genotypes they can detect. With the advent of next-generation sequencing (NGS) we can sidestep all those problems, as we can sequence whole tuberculosis genomes at increasingly smaller costs and requiring less and less DNA. In this review, we explain how accumulated knowledge in the field has allowed us to go from phenotypic testing to molecular methods to Whole Genome Sequencing (WGS) for resistance diagnostics. We compare current diagnostic methods with WGS as to their efficacy in detecting resistant cases, and show how forthcoming advances in NGS technologies will be crucial in widespread implementation of WGS as a diagnostic tool.
El diagnóstico de la tuberculosis resistente ha mejorado ampliamente en los últimos años gracias al desarrollo de pruebas estandarizadas de diagnóstico tanto fenotípicas como moleculares. Sin embargo, estas pruebas son o bien lentas o limitadas en el número de genotipos resistentes que son capaces de detectar. Con el auge de las nuevas tecnologías de secuenciación masiva podemos evitar esos problemas secuenciando el genoma completo cada vez a un coste más bajo y requiriendo cantidades menores de ADN. En esta revisión, explicamos cómo se ha podido progresar desde las pruebas fenotípicas a los métodos moleculares hasta la secuenciación del genoma completo para el diagnóstico de resistencias gracias a sucesivos descubrimientos en el campo. Comparamos la eficacia de la secuenciación del genoma completo para detectar casos resistentes con respecto a la de los métodos diagnósticos actuales, y mostramos cómo los avances futuros en esta tecnología serán cruciales para la implementación generalizada de esta herramienta diagnóstica.
An extreme expression of violence and sadism against women in Mexico is the increase in murders of women throughout the country. The causes of this violence are associated with the increase in ...extreme poverty, unemployment, the disintegration of the peasant economy, and social polarization imposed on the poor by neoliberal policies. Femicide and violence may therefore be considered components of the current structural crisis of the capitalist system.
The current crisis in Venezuela is sometimes said to have been provoked by the response of imperialism and the local oligarchy to the fundamental changes in economic and political relations fostered ...during the administrations of Hugo Chávez. A quantitative study using various statistical sources shows that the significant increase in oil rent during the Chávez presidency did not translate into a qualitative transformation in the form of state intervention and that, although social expenditures increased in that period, most of the income that allowed this was obtained through currency overvaluation by inefficient national and foreign capital. The current crisis is, therefore, evidence of the limits of low-productivity state and private capital reproduction due to the decline in oil prices rather than of a conflict between overcoming and reproducing capitalism in an alleged "economic war." A veces se dice que la crisis actual en Venezuela ha sido provocada por la respuesta del imperialismo y la oligarquía local a los cambios profundos en las relaciones económicas y políticas promovidos durante la administración de Hugo Chávez. Un estudio cuantitativo en el que se usaron diferentes fuentes estadísticas demuestra que el aumento significativo en la renta del petróleo durante la presidencia de Chávez no se tradujo en una transformación cualitativa de la intervención estatal y que, aunque los gastos sociales aumentaron en ese período, la mayor parte del ingreso que permitió ese aumento se obtuvo por medio de la sobrevaluación de la moneda por parte del ineficiente capital nacional y extranjero. Por lo tanto, la crisis actual es evidencia de los límites de la baja productividad de la reproducción estatal y privada debido a la caída en el precio del petróleo y no un conflicto entre la eliminación y la reproducción del capitalismo en una supuesta "guerra económica."
On Democratic Politics Norbert Lechner
Latin America Research Commons eBooks,
12/2023
eBook
Open access
The German-born, Chilean author Norbert Lechner remains one of Latin America’s most prominent and creative social scientists. His work is indebted to the intense debates regarding theories of ...modernization, developmentalism, and dependence that took place in Latin American intellectual and political circles. These theoretical sources were present as a cognitive horizon in his essential writings, and many of the central concerns that enlivened his oeuvre arose from his intellectual immersion in these deliberations. If the confrontations with the revolutionary discourses of the 1960s informed his vision of the Latin American state, his experience with authoritarianism led him to pose a question that would become central to all his career: What does it mean to do politics, and what does it mean to do democratic politics? This anthology, which includes the first translations into English of three of his most outstanding works can guide our readers, like Ariadne’s thread, through the intellectual output of this great thinker. It should also be said that these writings contain some of the most intellectually stimulating approaches to political sociology written in Latin America. Published between the 1980s and the first decade of the 2000s, the texts cover a span of more than thirty years during which the author developed a very personal vision as he sought to understand politics in a different way.
Efforts to develop a shared, Pan-American indigenista plan, beginning with the creation of the Inter-American Indian Institute (Instituto Indigenista Interamericano—III) in 1940, had to overcome a ...series of problems, especially financial and political ones. Obtaining support from the Mexican government and, above all, from the United States allowed the III to launch some important projects, but it greatly limited the extent to which it could promote a truly Pan-American program. The historical record suggests that, in the end, the radical and ambitious indigenista plan was hard to realize. Moreover, this history was much more uncertain, mixed, and ambivalent than had been expected and challenged long-held assumptions about indigenismo and its role. Con la creación del Instituto Indigenista Interamericano (III), en 1940, se pretendía elaborar un programa indigenista panamericano, pero había que superar una serie de problemas, sobre todo financieros y políticos. Gracias al apoyo inicial del gobierno mexicano y de los Estados Unidos, el III puso en marcha algunos proyectos importantes, pero ese mismo apoyo limitó, en buena medida, la posibilidad de promover un programa indigenista que fuera realmente panamericano. La evidencia histórica sugiere, de hecho, que este programa indigenista, ambicioso y radical, era de dificil realización. Además, su historia se revela mucho más incierta, incoherente y ambivalente de lo esperado, desafiando muchas de las ideas consolidadas sobre el indigenismo y su papel.
Despite running for a fourth term as president and winning in the first round in October 2019’s presidential elections, Evo Morales was violently overthrown in a civilian, police, and military coup. ...This event provided rationales for the leftist detractors of the MAS government to float the end-of-cycle theory with regard to Bolivia. Various perspectives were involved in this debate: the approach of the postextractivist/postdevelopmentalist left, the critique of the autonomist left, the approach of the doctrinaire/revolutionary left, and the perspective of the progressive left, which is sympathetic to the Morales government. Because of a lack of understanding of the reconfiguration under way of international dependency relations under neoliberalism, the end-of-cycle theory distorts reality, specifically with regard to Bolivian politics.
A pesar de postularse para un cuarto mandato como presidente y ganar en la primera vuelta de las elecciones presidenciales de octubre de 2019, Evo Morales fue derrocado violentamente en un golpe de estado civil, policial y militar. Este evento sirvió de base para que los detractores izquierdistas del gobierno del MAS plantearan la teoría del fin de ciclo con respecto a Bolivia. En este debate se involucraron varias perspectivas: el enfoque de la izquierda posextractivista/posdesarrollista, la crítica de la izquierda autonomista, el enfoque de la izquierda doctrinaria/revolucionaria y la perspectiva de la izquierda progresista, que de hecho simpatiza con el gobierno de Morales. Debido a la falta de comprensión en torno a la reconfiguración en curso de las relaciones de dependencia internacional bajo el neoliberalismo, la teoría del fin de ciclo distorsiona la realidad, particularmente en lo que respecta a la política boliviana.
After Fidel Castro's retirement from his main governmental positions, Cuba finds itself at a crossroads. Two main challenges emerge, one economic and one political. The economic one arises from the ...need to design a productive system that resolves the imbalance between workers' salaries and the actual distribution of basic goods and the imbalance between different sectors of society without destroying the revolution's social achievements. The political one must deal with the creation of a new form of governance and consensus building in the absence of the revolution's founder and leader. The changes to be introduced require the broadening of democracy. These challenges entail a national deliberation process during the Sixth Congress of the Cuban Communist Party that will identify several fundamental issues.
Liberation theology was very important in Latin America between 1970 and 1980. While it is less significant today, it has not disappeared. If we look at Colombia, we can see the pastoral and ...political commitment of the religious and the laity in various regions as they accompany marginalized communities, victims of government and parastatal violence, in conformity with their preferential option for the poor. Motivated by the crucified Christ, the heirs of liberation theology have developed a theology of life or of human rights. As human rights advocates, they identify among the causes of violence the policies of capitalist development, denounced as imperialist and responsible for the poverty of the majority of the population. This development has its origin in the parallel dynamics of social and international relations and the associated adaptation of the social movement. La teología de la liberación tuvo mucha importancia en América Latina entre los años 1970 y 1980. Bien que hoy ella sea menos relevante, no ha desaparecido. Si tomamos el caso de Colombia podemos ver el compromiso pastoral y político de laicos y religiosos presentes en diferentes regiones del país, quienes consecuentes ante su opción preferencial por los pobres están acompañando comunidades marginalizadas, víctimas de la violencia estatal y paraestatal. Inspirados en Jesús crucificado, los herederos de la teología de la liberación han hilado una teología de los derechos humanos o de la vida. Como defensores de derechos humanos, ellos identifican dentro de las causas de la violencia las políticas de desarrollo capitalista, denunciadas como imperialistas y como responsables de la miseria de las grandes mayorías. Esta trasformación se origina en la dinámica paralela de las relaciones sociales e internacionales y la adaptación consecuente del movimiento social.
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