Prevalence of non-communicable diseases among household contacts of people with tuberculosis: A systematic review and individual participant data meta-analysis.

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.

High all-cause mortality and increasing proportion of older adults with tuberculosis in Texas, 2008-2020.

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

Antigen specificity shapes antibody functions in tuberculosis.

Tuberculosis (TB) is the number one infectious disease cause of death worldwide due to an incomplete understanding of immunity. Emerging data highlight antibody functions mediated by the Fc domain as immune correlates. However, the mechanisms by which antibody functions impact the causative agent Mycobacterium tuberculosis (Mtb) are unclear. Here, we examine how antigen specificity determined by the Fab domain shapes Fc effector functions against Mtb. Using the critical structural and secreted virulence proteins Mtb cell wall and ESAT-6 & CFP-10, we observe that antigen specificity alters subclass, antibody post-translational glycosylation, and Fc effector functions in TB patients. Moreover, Mtb cell wall IgG3 enhances disease through opsonophagocytosis of extracellular Mtb . In contrast, polyclonal and a human monoclonal IgG1 we generated targeting ESAT-6 & CFP-10 inhibit intracellular Mtb . These data show that antibodies have multiple roles in TB and antigen specificity is a critical determinant of the protective and pathogenic capacity.

Proteomic analysis of lung responses to SARS-CoV-2 infection in aged non-human primates: clinical and research relevance.

With devastating health and socioeconomic impact worldwide, much work is left to understand the Coronavirus Disease 2019 (COVID-19), with emphasis in the severely affected elderly population. Here, we present a proteomics study of lung tissue obtained from aged vs. young rhesus macaques (Macaca mulatta) and olive baboons (Papio Anubis) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using age as a variable, we identified common proteomic profiles in the lungs of aged infected non-human primates (NHPs), including key regulators of immune function, as well as cell and tissue remodeling, and discuss the potential clinical relevance of such parameters. Further, we identified key differences in proteomic profiles between both NHP species, and compared those to what is known about SARS-CoV-2 in humans. Finally, we explored the translatability of these animal models in the context of aging and the human presentation of the COVID-19.

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 have 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 given DM was 2.7-fold 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 this COVID-19/DM/latent TB high-risk group.

Human alveolar lining fluid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells.

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host-cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated M.tb growth within human alveolar macrophages. Here we determined the impact of human ALF on M.tb infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed M.tb had significantly increased intracellular growth with rapid replication in ATs compared to adult ALF (A-ALF)-exposed bacteria, as well as a dampened inflammatory response. A potential mechanism underlying this accelerated growth in ATs was our observation of increased bacterial translocation into the cytosol, a compartment that favors bacterial replication. These findings in the context of our previous studies highlight how the oxidative and dysfunctional status of the elderly lung mucosa determines susceptibility to M.tb infection, including dampening immune responses and favoring bacterial replication within alveolar resident cell populations, including ATs, the most abundant resident cell type within the alveoli.

Nuevas herramientas para la detección de la tuberculosis latente

La tuberculosis es un problema serio de salud pública en el mundo, especialmente en países en vía de desarrollo, inclusive Colombia. En nuestro país estamos enfocados en el manejo clínico de los pacientes con tuberculosis activa, pero no hay campañas efectivas que identifiquen y provean terapia a los individuos con las formas latentes de la infección y con alto riesgo de progresar hacia la enfermedad. En esta revisión se plantea la importancia de realizar dichas campañas para evitar la diseminación de la infección en la comunidad. Esto incluye la búsqueda activa y el tratamiento profiláctico de los contactos de casos recientes, así como la de individuos con tuberculosis latente con alto riesgo de desarrollar la enfermedad. En ausencia de una prueba de oro para detectar la tuberculosis latente, la prueba cutánea de la tuberculina se ha utilizado por más de 100 años para dicho fin, a pesar de sus limitaciones de sensibilidad y especificidad. En esta revisión se evalúan las ventajas y desventajas de una nueva generación de inmunoensayos que incluye la prueba comercial Quantiferon y el desarrollo experimental del ELISPOT. Ambas se basan en la detección de IFN ©secretado por linfocitos de sangre periférica cuando se incuban con antígenos específicos del bacilo tuberculoso. Finalmente, se plantea la importancia de desarrollar pruebas moleculares enfocadas en detectar el ADN de la micobacteria como posible complemento a los inmunoensayos descritos.

New tools for detection of latent tuberculosis Tuberculosis is a serious public health problem worldwide, particularly in developing countries. In Colombia, the focus is on the clinical management of patients with active disease, but not on preventive programs that identify and treat individuals with a latent tuberculosis infection. This review emphasized the importance of preventative programs and their critical role in the curtailment of infection dissemination in the community. An effective program includes chemoprophylactic treatment of household contacts and detection of individuals with latent tuberculosis infection and with high risk of reactivation of disease. The tuberculin skin test has been used effectively for more than 100 years, despite inherent sensitivity and specificity limitations. Herein the advances provided by a new generation of immunoassays are reviewed, includingthe commercially-available Quantiferon and the experimental development of ELISPOT. Both are based on the detection of IFN....secretion by peripheral T cells upon incubation with Mycobacterium tuberculosis antigens. Finally, the importance of molecular techniques aimed at detecting DNA from the mycobacterium is discussed as a possible complement to the described immunoassays. New tools for detection of latent tuberculosis Tuberculosis is a serious public health problem worldwide, particularly in developing countries. In Colombia, the focus is on the clinical management of patients with active disease, but not on preventive programs that identify and treat individuals with a latent tuberculosis infection. This review emphasized the importance of preventative programs and their critical role in the curtailment of infection dissemination in the community. An effective program includes chemoprophylactic treatment of household contacts and detection of individuals with latent tuberculosis infection and with high risk of reactivation of disease. The tuberculin skin test has been used effectively for more than 100 years, despite inherent sensitivity and specificity limitations. Herein the advances provided by a new generation of immunoassays are reviewed, includingthe commercially-available Quantiferon and the experimental development of ELISPOT. Both are based on the detection of IFN....secretion by peripheral T cells upon incubation with Mycobacterium tuberculosis antigens. Finally, the importance of molecular techniques aimed at detecting DNA from the mycobacterium is discussed as a possible complement to the described immunoassays.

El papel de los carbohidratos en la antigenicidad de las glicoproteínas del cisticerco de la Taenia solium / Hydrocarbon role in Taenia solium cysticercus glycoproteins antigenicity

La neurocisticercosis es una infección causada por el cisticerco de la T. Solium y puede confundirse con otras afecciones del sistema nervioso central. Las glicoproteínas de 12-28 kD de este parásitos son útiles para el diagnóstico serológico de la neurocisticercosis. Estas glicoproteínas contiene abundantes carbohidratos asociados vía asparagina (tipo N). Objetivo: Determinar la contribución de los carbahidratos tipo N en la antigenicidad de las glicoproteínas. Materiales y Métodos: se purificaron las glicoproteínas de 12, 16 y 18 kD de los cisticercos utilizando un gel preparativo de poliacrilamida y se sometieron a deglicosilación enzimática con PNGase F. Luego se evaluaron los cambios en antigenicidad entre las proteínas nativas y deglicosiladas por Western blot. Resultados: los antígenos deglicosilados redujeron su peso molecular a 7 kD y perdieron parte de su antigenicidad. Esta reducción fue más notoria para la proteína de 18 kD. La cual tiene mayor contenido de carbohidratos que la de 12 y 16 kD. Conclusión: estos resultados sugieren que los carbohidratos no sólo contribuyen a la antigenicidad, sino que además causan un bloqueo estérico que inhibe que el sistema inmune detecte otros epítopes no expuesto. Estos datos sugieren que la antigenicidad de las glicoproteínas de T. Solium se debe a una combinación de epítopes sacarídicos y probablemente proteicos