Detection of Mycobacterium bovis in Free-Ranging Sapajus nigritus, Argentina.

Mycobacterium bovis and Mycobacterium tuberculosis are the most relevant among pathogenic mycobacteria, both belonging to the M. tuberculosis complex (MTC). Samples of blood, liver, spleen, kidneys, lungs and caseous tubercles were collected from a free-ranging juvenile black capuchin monkey (Sapajus nigritus) showing non-specific signs of illness. Macroscopic findings included emaciation, a caseous lesion in a tooth and gingiva, disseminated nodules in both lungs and left kidney parenchyma and caseous nodules on the pleura and mesentery. The lesions suggested MTC infection, a diagnosis subsequently supported in the lung by bacilloscopy, immunochromatography and PCR. A multiplex PCR further validated the presence of M. bovis genes. Cases of tuberculosis in platyrrhine primates have only been reported in animals maintained in captivity. We describe for the first time the pathological and molecular findings of M. bovis infection in a free-ranging platyrrhine monkey within an area of intense human-wildlife interaction, which has important implications from a One Health perspective.

Pharmacogenetics of tuberculosis treatment toxicity and effectiveness in a large Brazilian cohort.

BACKGROUND: Genetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil. METHODS: Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil. We included persons with culture-confirmed drug-susceptible pulmonary tuberculosis who started treatment between 2015 and 2019, and who were eligible for pharmacogenetics. Treatment included 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol, then 4 months of isoniazid and rifampin or rifabutin, with 24-month follow-up. Analyses included 43 polymorphisms in 20 genes related to antituberculosis drug hepatotoxicity or pharmacokinetics. Whole exome sequencing was done in a case-control toxicity subset. RESULTS: Among 903 participants in multivariable genetic association analyses, NAT2 slow acetylator status was associated with increased risk of treatment-related grade 2 or greater adverse events, including hepatotoxicity. Treatment failure/recurrence was more likely among NAT2 rapid acetylators, but not statistically significant at the 5% level. A GSTM1 polymorphism (rs412543) was associated with increased risk of treatment-related adverse events, including hepatotoxicity. SLCO1B1 polymorphisms were associated with increased risk of treatment-related hepatoxicity and treatment failure/recurrence. Polymorphisms in NR1/2 were associated with decreased risk of adverse events and increased risk of failure/recurrence. In whole exome sequencing, hepatotoxicity was associated with a polymorphism in VTI1A , and the genes METTL17 and PRSS57 , but none achieved genome-wide significance. CONCLUSION: In a clinical cohort representing three regions of Brazil, NAT2 acetylator status was associated with risk for treatment-related adverse events. Additional significant polymorphisms merit investigation in larger study populations, particularly regarding risk of treatment failure/recurrence.

Tuberculosis preventive treatment in newborns.

OBJECTIVE: To describe the reported cases of newborns subjected to tuberculosis preventive treatment (TPT) in the state of Paraná, Brazil, and to evaluate the safety and effectiveness in preventing the progression of TB disease in this population. METHOD: Observational, descriptive case series, with secondary data. The characteristics of the participants were analyzed from the information systems of preventive treatment of TB (of Paraná), between 2009 and 2016. To evaluate which children had developed tuberculosis later or died, we used the data from the information systems of TB (in Brazil), and mortality (in Paraná), covering the years 2009 to 2018. RESULTS: A total of 24 children underwent TPT with the age at treatment onset ranging from 0 to 87 days (median: 23 days). In 95.8 %, the exposure occurred at home, and in 33.3 % of cases, the mother was the source of the infection. A total of 20.8 % of the children tested positive for tuberculosis test at 3 months of age, 83.3 % completed treatment, and 2 experienced adverse events (gastrointestinal issues). No children developed TB or died during the minimum of a 2-year evaluation period through the official databases. CONCLUSIONS: In this case series, the adherence to the plan was high, with few adverse events and 100 % protection against infection.

Evaluation of nonpolar lipid extract antigen-based enzyme-linked immunosorbent assay for the serodiagnosis of tuberculosis.

This study assessed the diagnostic potential of nonpolar lipid extracts in enzyme-linked immunosorbent assays (ELISAs) for tuberculosis (TB) serodiagnosis. Nonpolar lipid extracts were harvested from Mycobacterium tuberculosis (Mtb) knockout in mce1 operon (∆mce1) and its parental wild type (WT) strains. IgM and IgG anti-nonpolar lipid serum levels were measured in TB patients (n=45), healthy individuals with positive (n=22) and negative (n=44) interferon-gamma release assay (IGRA) results, and symptomatic respiratory (SR) patients with negative TB tests (n=9). IgG anti-WT lipid distinguished TB patients from IGRA-positive individuals with 60% sensitivity and 77.3% specificity. Conversely, IgG anti-∆mce lipid levels didn't vary significantly across groups. Interestingly, most SR patients exhibited significantly higher IgM and IgG anti-WT lipid titers than the IGRA-positive and -nega groups. While the overall diagnostic potential of Mtb nonpolar lipids was limited, the impaired immunogenecity of Δmce1 lipid extract suggests that some missing lipid classes in this extract can potentially induce antibody production in TB patients.

18F-FDG PET/CT Incidental Finding of Rare Extrapulmonary Presentation of Mycobacterium tuberculosis.

ABSTRACT: A 41-year-old woman presented with a left breast mass for which mammography was performed. Mammogram revealed a suspicious BI-RADS 4, palpable left breast mass with associated nipple retraction. As malignancy was suspected, the patient underwent breast MRI and 18F-FDG PET/CT for staging. Multiple ultrasound guided biopsies were then performed of the left breast, left axillary lymph nodes, and left cervical lymph nodes. Final pathology was negative for malignancy, but final cultures grew Mycobacterium tuberculosis (Tb). The patient was initially intolerant to frontline medications, but eventually successfully treated with isoniazid, ethambutol, pyrazinamide, and moxifloxacin, as demonstrated by posttreatment mammography.

Interaction between type 2 diabetes and past COVID-19 on active tuberculosis.

BACKGROUND: The global setback in tuberculosis (TB) prevalence and mortality in the post-COVID-19 era has been partially attributed to pandemic-related disruptions in healthcare systems. The additional biological contribution of COVID-19 to TB is less clear. The goal of this study was to determine if there is an association between COVID-19 in the past 18 months and a new TB episode, and the role played by type 2 diabetes mellitus (DM) comorbidity in this relationship. METHODS: A cross-sectional study was conducted among 112 new active TB patients and 373 non-TB controls, identified between June 2020 and November 2021 in communities along the Mexican border with Texas. Past COVID-19 was based on self-report or positive serology. Bivariable/multivariable analysis were used to evaluate the odds of new TB in hosts with past COVID-19 and/or DM status. RESULTS: The odds of new TB were higher among past COVID-19 cases vs. controls, but only significant among DM patients (aOR 2.3). The odds of TB in people with DM was 2.7-fold higher among participants without past COVID-19 and increased to 7.9-fold among those with past COVID-19. CONCLUSION: DM interacts with past COVID-19 synergistically to magnify the risk of TB. Latent TB screening and prophylactic treatment, if positive, is recommended in past COVID-19 persons with DM. Future studies are warranted with a longitudinal design and larger sample size to confirm our findings.

The effect of breathing exercises on fatigue in tuberculosis patients: a randomized controlled trial.

OBJECTIVE: This study was conducted as a randomized controlled trial to investigate the effect of breathing exercises on fatigue in patients diagnosed with tuberculosis. METHODS: The tuberculosis patients included in the study were divided into two groups: intervention (26) and control (28) by a program established after the power analysis. After the researcher informed the patients in the intervention group about breathing exercises, including diaphragmatic and pursed lip breathing, they were taught, and the first exercise was practiced. Then, the patients in this group did breathing exercises once a day in the morning, 3 days a week, for a total of 4 weeks, with the researcher using the online interview method. The data were collected using a questionnaire and the Piper Fatigue Scale. The total score of the Piper Fatigue Scale ranges from 0 to 10, and the higher the score, the higher the fatigue level. The Piper Fatigue Scale was repeated at the end of the fourth week in both groups. RESULTS: Patients in the intervention group (88.5%) and control group (85.7%) reported that they were tired after the diagnosis of tuberculosis. The Piper Fatigue Scale total mean score of the intervention group was 8.29±1.19 before the intervention and dropped to 6.83±1.02 at the fourth week (p<0.05), whereas the Piper Fatigue Scale total mean score of the control group was 7.88±1.09 before the intervention and 7.93±1.02 at the fourth week (p>0.05). CONCLUSION: Breathing exercises done by tuberculosis patients were found to lower their levels of fatigue. Accordingly, it is recommended to benefit from breathing exercises, which are effective, inexpensive, and easy to apply in the management of fatigue. CLINICAL TRIAL REGISTRATION NUMBER: The study was registered with clinicaltrial.gov NCT05202431.

Enhancing Knowledge and Beliefs: The Impact of a Gender-transformative Training Program on Tuberculosis Care in Southern Nigeria.

BACKGROUND: Gender-related barriers significantly impede care-seeking for tuberculosis (TB), leading to poor treatment outcomes. This study aimed to assess changes in knowledge and beliefs following a training program on gender-transformative TB programming among stakeholders in Southern Nigeria. METHODS: A cross-sectional pretest/posttest design was employed to evaluate the training's effectiveness among participants from September 2023 to March 2024. A 2-day training session was conducted using a standardized training manual. Participants included members of TB civil society organizations and other relevant stakeholders. A standardized questionnaire was administered before and after the training. RESULTS: Of the 304 respondents, 160 (52.6%) were aged 40 years or younger, with a mean age of 39.6 (±10.5) years; 184 (60.5%) were female. The mean pretest knowledge score was 7.20 (±1.16), which increased to 8.44 (±1.12) posttraining (t = -15.20; P < 0.001). Similarly, the mean score for the gender responsiveness to the TB programming scale improved from 30.6 (±5.4) pretest to 32.8 (±4.9) posttest (P < 0.001). CONCLUSION: The training significantly enhanced stakeholders' knowledge of TB and their understanding of gender responsiveness in TB programming. These findings underscore the necessity for ongoing sensitization of TB service providers and the promotion of TB education and stigma reduction efforts to ensure gender-responsive and inclusive TB service delivery. Continuous awareness initiatives are essential to challenge deep-rooted negative sociocultural beliefs and gender norms affecting TB programming.

Risk of mycobacterial infections in a cohort of silicosis patients with autoimmune rheumatic diseases.

OBJECTIVE: To evaluate the incidence rates of mycobacterial infections in silicosis patients with systemic autoimmune rheumatic disease (ARD). METHODS: This was a retrospective cohort of silicosis patients between January of 1999 and December of 2023. We compared the incidence of tuberculosis and nontuberculous mycobacterial disease (NTM) in patients with silicosis with and without ARD. We also compared the tuberculosis incidence in the overall cohort with general Brazilian population estimates. RESULTS: The study comprised 369 silicosis patients, of whom 35 (9.5%) had ARD. Having ARD did not affect the cumulative incidence of mycobacterial diseases. The risk of tuberculosis was higher in the cohort when compared with that in the adult Brazilian male population (age-adjusted incidence rate ratio = 20.46; 95% CI 14.89-28.13). CONCLUSIONS: In this cohort of patients with silicosis, ARD was not associated with the incidence of mycobacterial diseases.

Unveiling the Antimycobacterial Potential of Novel 4-Alkoxyquinolines: Insights into Selectivity, Mechanism of Action, and In Vivo Exposure.

This work presents a comprehensive investigation into the design, synthesis, and evaluation of a novel series of 4-alkoxyquinolines as potential antimycobacterial agents. The design approach, which combined molecular simplification and chain extension, resulted in compounds with potent and selective activity against both drug-susceptible and multidrug-resistant Mycobacterium tuberculosis strains. The lead molecule, targeting the cytochrome bc1 complex, exhibited favorable kinetic solubility and remarkable chemical stability under acidic conditions. Despite in vitro ADME evaluations showing low permeability and high metabolism in rat microsomes, the lead compound exhibited bacteriostatic activity in a murine macrophage model of TB infection and demonstrated promising in vivo exposure following gavage in mice, with an AUC0-t of 127.5 ± 5.7 µM h. To the best of our knowledge, for the first time, a simplified structure from 2-(quinolin-4-yloxy)acetamides has shown such potential. These findings suggest a new avenue for exploring this chemical class as a source of antituberculosis drug candidates.

Repercussions of the pandemic on tuberculosis control actions from the perspective of health professionals.

OBJECTIVES: to analyze the repercussions of the COVID-19 pandemic on tuberculosis control actions from the perspective of primary health care professionals. METHODS: this descriptive study with a qualitative approach was conducted from November 2022 to April 2023, using semi-structured interviews with 11 key informant professionals from primary health care units in a Brazilian capital. Data were organized using Atlas.ti 22.0 software and subjected to thematic-categorical content analysis. RESULTS: the pandemic scenario caused alterations in the work process, necessitating abrupt adaptations, and led to detrimental impacts on the health of professionals and tuberculosis control actions, which were reduced or discontinued. FINAL CONSIDERATIONS: there was evident unpreparedness and a lack of resources from various governmental levels and health services to handle the public health emergency situation without severe harm to the provision of essential services.

Characteristics and outcomes of in-hospital patients with Covid-19 and history of tuberculosis: a matched case-control from the Brazilian Covid-19 Registry.

BACKGROUND: The Covid-19 pandemic caused a negative impact on other infectious diseases control, prevention, and treatment. Consequently, low and middle-income countries suffer from other endemic diseases, such as tuberculosis. This study was designed to compare Covid-19 manifestations and outcomes between patients with previously treated tuberculosis and controls without this condition. METHODS: We performed a matched case-control study drawn from the Brazilian Covid-19 Registry data, including in-hospital patients aged 18 and over with laboratory-confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with a past history of tuberculosis. Controls were Covid-19 patients without a tuberculosis history. Patients were matched by hospital, sex, presence of HIV, and number of comorbidities, with a 1:4 ratio. RESULTS: Of 13,636 patients with laboratory-confirmed diagnoses of Covid-19 enrolled in this study, 80 had a history of tuberculosis. Statistical differences in history of chronic pulmonary obstructive disease (15% vs. 3.2%), psychiatric disease (10% vs. 3.5%,), chronic kidney disease (11.2% vs. 2.8%), and solid-organ transplantation; (5% vs. 0.9%, p < 0.05 for all) were higher in patients with a past history of tuberculosis. Prior use of inhalatory medications (5% vs. 0.6%,), oral corticoids (8.8% vs. 1.9%), immunosuppressants (8.8% vs. 1.9%,) and the use of illicit drugs were more common in the case group (6.2% vs. 0.3% p < 0.05for all). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis, and ICU admission. CONCLUSIONS: Patients with a history of tuberculosis infection presented a higher frequency of use of illicit drugs, chronic pulmonary obstructive disease, psychiatric disease, chronic kidney disease, solid-organ transplantation, prior use of inhalatory medications, oral corticoids, and immunosuppressants. The outcomes were similar between cases and controls.

Laboratory validation of a simplified DNA extraction protocol followed by a portable qPCR detection of M. tuberculosis DNA suitable for point of care settings.

Tuberculosis, caused by Mycobacterium tuberculosis, is a treatable and curable disease, and yet remains one of the leading causes of death worldwide. Diagnosis is essential to reducing the number of cases and starting treatment, but costly tests and equipments that require complex infrastructure hamper their widespread use as a tool to contain the disease in vulnerable populations as well countries lacking resources. Therefore, it becomes necessary to develop new technological approaches to molecular methods as well as screening tests that can be rapidly conducted among people presenting to a health facility to differentiate those who should have further diagnostic evaluation for TB from those who should undergo further investigation for non-TB diagnoses. The present study aimed to evaluate two experimental DNA extraction methods from clinical samples (FTA card versus sonication) followed by analysis in a portable qPCR instrument (the Q3-plus). The FTA card-based protocol showed 100% sensitivity and specificity, while the sonication protocol showed 80% sensitivity and 89% specificity when compared to the traditional gold standard culture. The portable protocol, comprised by the FTA card method and the portable instrument Q3-Plus, showed sensitivity and specificity of 92% and 61%, respectively, when compared to culture, and 75% and 81%, respectively, when compared to the standard TB case classification. The ROC curve showed an AUC of 0.78 (p<0.001) for the portable protocol and 0.93 (p<0.001) for the GeneXpert Ultra. The limit of detection (LOD) for Mycobacterium tuberculosis (H37Rv strain) detection in spiked samples obtained using the portable protocol (FTA card and Q3-Plus) was 19.3 CFU/mL. As an added benefit, using the FTA card facilitates sample handling, transport, and storage. It is concluded that the use of the FTA card protocol and the Q3-Plus yields similar sensitivity and specificity as the gold standard diagnostic tests and case classification. We suggest that the platform is suitable to use as a point of care tool, assisting in the screening of tuberculosis in hard-to-reach or resource-limited areas.

La categorización como instrumento valorativo del control de la tuberculosis / Categorization as an Assessment Tool for Tuberculosis Control

Introducción: El control de la tuberculosis requiere procesos renovados de monitoreo y evaluación.Objetivo: Analizar la notificación y las brechas de la tuberculosis en países latinoamericanos y caribeños en 2021.Métodos: Aplicación de un modelo renovado de categorización del control utilizando las tasas de notificación de casos de cada país y las brechas con relación a las tasas estimadas. La versión simplificada contiene siete categorías y la detallada incluye subcategorías. Se calcularon los porcentajes y la mediana de las tasas de los países para cada categoría simplificada, el menor valor fue referencia para calcular las diferencias absolutas y relativas. A partir de la razón de detección, se aplicó una escala de calificación y se obtuvo la correlación entre las tasas de notificación. Las categorías de control insuficiente fueron contrastadas con las categorías de control casi-satisfactorio, control satisfactorio y ultracontrol. Resultados: De los 40 países que notificaron casos de tuberculosis a la OMS en 2021, 15 (37,5%) estaban en la categoría de control insuficiente; 2 (5%) en pre-eliminación y 4 (10%) en eliminación. La desigualdad absoluta fluctuó desde 31,8 por 100.000 en control insuficiente hasta 2,5 en ultra-control, mayor que en la referencia. La correlación realizada fue débil, al encontrarse los puntos de la dispersión alejados de la recta y más cercanos a cero. Conclusiones: La categorización puede aplicarse a todos los países y al interior de ca-da uno para valorar el progreso "paso a paso" del control hacia la eliminación de la tuberculosis como problema de salud pública.

Introduction: Tuberculosis control requires renewed monitoring and evaluation processes. Objective: To analyse tuberculosis notification and gaps in Latin American and Caribbean countries in 2021.Methods: Application of a revamped control categorisation model using each country's case notification rates and gaps in relation to estimated rates. The implified version contains seven categories and the detailed version includes subcategories. Percentages and median country rates were calculated for each simplified category, the lowest value being the reference for calculating absolute and relative differences. From the detection ratio, a rating scale was applied and the correlation between reporting rates was obtained. The categories of poor control were contrasted with the categories of near-satisfactory control, satisfactory control and ultracontrol.Results: Of the 40 countries that reported tuberculosis cases to WHO in 2021, 15 (37.5%) were in the poor control category; 2 (5%) in pre-elimination and 4 (10%) in eli-mination. The absolute inequality ranged from 31.8 per 100,000 in insufficient control to 2.5 in ultra-control, higher than the baseline. The correlation performed was weak, as the points of the dispersion were far from the straight line and closer to zero. Conclusions: The categorisation can be applied across and within countries to assess 'step-by-step' progress in control towards elimination of tuberculosis as a public health problem.

Actualizaciones clave sobre el tratamiento de la tuberculosis farmacorresistente. Comunicación rápida

Esta es una comunicación rápida que se publica antes de la actualización de las directrices consolidadas de la Organización Mundial de la Salud (OMS) prevista para principios del 2025, con el fin de informar a los programas nacionales de tuberculosis (TB) y a otras partes interesadas de los cambios clave en el tratamiento de la DR-TB y permitir una transición y una planificación rápidas a nivel nacional. Las directrices basadas en la evidencia más recientes sobre el tratamiento de la TB y la TB farmacorresistente, incluida la TB-RR/MDR y la TB pre-XDR, fueron publicadas por la OMS en mayo del 2022 (Directrices unificadas de la OMS sobre la tuberculosis). Es necesario el acceso a los esquemas de tratamiento y a los medicamentos más eficaces para optimizar los resultados del tratamiento al tiempo que se reducen al mínimo los eventos adversos, se mejora la tolerabilidad y la calidad de vida, y se previene la aparición de nuevas farmacorresistencias. En los últimos años han aparecido varios medicamentos nuevos y esquemas acortados (de 4 o 6 meses) que la OMS recomienda para el tratamiento de la TB y la TB-DR. En los últimos años, los investigadores han estado probando combinaciones y duraciones del uso de medicamentos para tratar la TB-RR/MDR que aún no han sido evaluadas por un grupo de elaboración de directrices de la OMS. Entre estos tratamientos se encuentra un nuevo esquema de 6 meses con bedaquilina (B), delamanid (D) y linezolid (L) en combinación con levofloxacina (Lfx), clofazimina (C) o ambos (ensayo clínico BEAT sobre la TB en Sudáfrica, NCT04062201) y un grupo de esquemas de 9 meses para el tratamiento de personas con TB-RR/MDR sin resistencia a las fluoroquinolonas (ensayo clínico endTB, NCT02754765). La evidencia obtenida en estos ensayos se ha notificado a la OMS, y se convocó un grupo de elaboración de directrices para examinar esta nueva evidencia sobre el tratamiento de la TB-RR/MDR y la TB pre XDR, con el fin de garantizar el acceso de las personas que reúnen los criterios para las opciones de tratamiento más recientes. Estas actualizaciones incluyen un nuevo régimen de 6 meses basado en bedaquilina (B), delamanida (D) y linezolid (L), en combinación con levofloxacino (Lfx) o clofazimina (C), o ambos, y un grupo de regímenes de 9 meses para el tratamiento de pacientes con TB-MDR/RR sin resistencia a las fluoroquinolonas.

Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis.

Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.06, 95%CI: 4.87 - 20.77, P = 7.92 × 10-8) in the FLOT1 gene and a subclavaluee of Mtb Lineage 2. In a human macrophage infection model, we observe hosts with the rs3130660-A allele exhibited stronger interferon gene signatures. The interacting strains have altered redox states due to a thioredoxin reductase mutation. We investigate this association in a 2020 cohort of 699 patients recruited during the COVID-19 pandemic. While the prevalence of the interacting strain almost doubled between 2010 and 2020, its infection is not associated with rs3130660 in this recent cohort. These findings suggest a complex interplay among host, pathogen, and environmental factors in tuberculosis dynamics.

Intravenous BCG vaccination in non-human primates induces superior serum antibody titers with enhanced avidity and opsonizing capacity compared to the intradermal route.

A new and more effective tuberculosis (TB) vaccine is urgently needed, but development is hampered by the lack of validated immune correlates of protection. Bacillus Calmette Guérin (BCG) vaccination by the aerosol (AE) and intravenous (IV) routes has been shown to confer superior levels of protection from challenge with Mycobacterium tuberculosis (M.tb) in non-human primates (NHP) compared with standard intradermal (ID) administration. This finding offers a valuable opportunity to investigate which aspects of immunity are associated with improved control of M.tb and may represent biomarkers or correlates of protection. As TB vaccine research to date has focused largely on cellular immunity, we aimed to better characterize the poorly-understood serum antibody response to BCG administered by different routes of vaccination in NHP. We demonstrate superior M.tb-specific IgG, IgA, and IgM titers in serum following IV BCG vaccination compared to the ID or AE routes. We also observe improved capacity of IgG induced by IV BCG to opsonize the surface of mycobacteria, and report for the first time that M.tb-specific IgG from IV BCG vaccinated animals is of higher avidity compared with IgG from ID or AE BCG vaccinated animals. Notably, we identified a significant correlation between IgG avidity and measures of protection from aerosol M.tb challenge. Our findings highlight a potential role for antibodies as markers and/or mediators of the superior vaccine-induced protection IV BCG confers against TB and suggest that quality, as well as quantity, of antibodies should be considered when developing and evaluating TB vaccine candidates.

[Tuberculosis: Analysis of the history and development of multiple antibiotic resistance]. / Tuberculosis: análisis de la historia y generación de múltiple resistencia a antibióticos.

Tuberculosis is an ancient disease that has accompanied humanity for the last three thousand years and is considered the oldest infectious disease that still exists. The Mycobacterium tuberculosis bacillus was spread worldwide due to human migrations, and there is archaeological evidence of spinal tuberculosis cases in Egyptian and Andean mummies, as well as texts that attributed the disease to social factors before suspecting its infectious nature. Throughout its history, humans have dealt with this pathology by developing unusual and ineffective therapies, leading to a significant increase in the disease's mortality. In the past century, the first antibiotics were introduced, bringing hope to eradicate this disease. However, evolutionary pressure has led to the emergence of multi-drug-resistant strains. Today, the development of computational techniques, such as artificial intelligence, has given us new hope for generating drugs and potential immunomodulatory therapies. However, it is essential to remember that those who do not know their history are doomed to repeat it. In this review, we summarize the history of tuberculosis, analyzing theories of its possible origin, its discovery, the creation of the first empirical treatments, vaccines, the emergence of new antibiotics, and how the mycobacterium quickly develops resistance.

La tuberculosis es una enfermedad ancestral que ha acompañado a la humanidad por los últimos tres mil años, y es considerada la enfermedad infecciosa más antígua que aún existe. El bacilo de Mycobacterium tuberculosis fue esparcido por todo el mundo gracias a las migraciones humanas, y existe evidencia arqueológica de casos de tuberculosis espinal en momias de Egipto y en la región andina, así como textos que atribuyen la enfermedad a factores sociales, antes de sospechar su carácter infeccioso. Durante toda su historia, el humano ha lidiado con esta patología, desarrollando terapias inusuales poco efectivas, lo cual llevó a un aumento importante de la mortalidad de la enfermedad. En el siglo pasado se introdujeron los primeros antibióticos y con ellos la esperanza de erradicar a esta enfermedad, sin embargo, la presión evolutiva ha hecho surgir cepas con multirresistencia a los fármacos. Hoy en día, el desarrollo de técnicas informáticas, como la inteligencia artificial, nos ha dado nuevas esperanzas para la generación de fármacos y posibles terapias inmunomoduladoras. Sin embargo, es importante tener en cuenta que el hombre que no conoce su historia está condenado a repetirla. En la presente revisión hacemos un resumen de la historia de la tuberculosis, analizando desde las teorías de su posible origen hasta su descubrimiento, la creación de los primeros tratamientos empíricos, vacunas, y surgimiento de nuevos antibióticos, así como la forma en la que la micobacteria crea rápidamente resistencia.

Factors associated with deaths by tuberculosis in the state of Mato Grosso, 2011-2020: retrospective cohort study.

OBJECTIVE: To investigate factors associated with tuberculosis deaths in Mato Grosso state, Brazil, from 2011 to 2020. METHODS: Retrospective cohort study with data obtained from the Notifiable Health Conditions Information System and the Mortality Information System. Deaths were qualified using probabilistic linkage and analyzed using Poisson regression. RESULTS: 12,331 cases and 525 deaths were identified over 10 years. The factors associated with death were: age ≥60 years (RR: 7.70; 95%CI 1.91;31.04), incomplete elementary and high school education (RR: 3.66; 95%CI 1.34;9.96), illiteracy (RR: 4.50; 95%CI 1.60;12.66), homeless population (RR: 2.41; 95%CI 1.34;4.35), alcohol use (RR: 1.45; 95%CI 1.04;2.02), male sex (RR: 1.48; 95%CI 1.04;2.09) and tobacco use (RR: 1.32; 95%CI 0.98;1.77). Laboratory confirmation was a protective factor. CONCLUSION: Risk of death was higher in men over 60 years old, with low education levels, in vulnerable situations, and who used alcohol/tobacco.

MAIN RESULTS: Risk of death was higher in the elderly, males, people with low education levels, homeless people, alcohol and tobacco users. Laboratory confirmation was a protective factor. IMPLICATIONS FOR SERVICES: Raising awareness of health professionals regarding risk factors, especially regarding risk behaviors and laboratory confirmation of tuberculosis, to which efforts should be targeted. PERSPECTIVES: It would be strategic to study survival in order to assimilate the effect of time and to study people with drug-resistant tuberculosis in order to update treatment recommendations. Health service managers need to define public policies aimed at the determinants found.

Clinical epidemiological and laboratory investigation in co-infection with COVID-19 and tuberculosis.

Currently, COVID-19 and tuberculosis (TB) are the deadliest infectious diseases worldwide. Their synergy, form of presentation, morbidity, and mortality are data that have been scarcely explored. Thus, this study aimed to characterize the clinical, epidemiological, and laboratory factors of this co-infection and to analyze the factors associated with the active TB among COVID-19 cases. A case-control study was conducted with a retrospective survey of 21 laboratory-confirmed COVID-19/TB co-infected patients (case group) and 21 COVID-19 patients (control group). The study included participants from eight hospitals in Campo Grande city, capital of Mato Grosso do Sul State, Brazil, from March 2020 to March 2022. Association analysis and binomial logistic regression were employed with statistical significance set at p≤0.05. From the 21 identified cases of COVID-19/TB co-infection, we found a more frequent association with HIV infection than the control-group, without worsening the outcome. COVID-19/TB patients had less dyspnea and less need for mechanical ventilation compared to the cases with COVID-19 only. On the other hand, COVID-19/TB patients had higher levels of C-reactive protein and lower hemoglobin levels, the latter variable was independently associated with COVID-19/TB. Among the clinical differences presented among COVID-19/TB co-infected patients, despite the association with HIV and lower clinical repercussions, only lower hemoglobin levels were associated with COVID-19/TB.