Nos2-/- mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis.

BACKGROUND: Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. METHODS: We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2-/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. RESULTS: Intra-cerebroventricular infection of Nos2-/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2-/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. CONCLUSIONS: Intra-cerebroventricular infection of Nos2-/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

COVID-19, the escalation of diabetes mellitus and the repercussions on tuberculosis.

The COVID-19 pandemic has significantly disrupted global tuberculosis (TB) control efforts. The mobilization of healthcare resources and personnel to combat the pandemic, and the nationwide lockdown measures resulted in an accumulation of a large number of undiagnosed TB cases. Exacerbating the situation, recent meta-analyses showed that COVID-19-induced diabetes mellitus (DM) is on the increase. DM is an established risk factor for TB disease and worsens outcomes. Patients with concurrent DM and TB had more lung cavitary lesions, and are more likely to fail TB treatment and suffer disease relapse. This may pose a significant challenge to TB control in low- and middle-income countries where a high TB burden is found. There is a need to step up the efforts to end the TB epidemic, which include increased screening for DM among patients with TB, optimizing glycemic control among patients with TB-DM, and intensifying TB-DM research to improve treatment outcomes for patients with TB-DM.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study.

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study / Medidas de confinamento específicas de cada país em resposta à pandemia de COVID-19 e seu impacto no controle da tuberculose: um estudo global

ABSTRACT The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

RESUMO O objetivo deste estudo foi descrever as medidas de confinamento específicas de cada país e os indicadores de tuberculose coletados durante o primeiro ano da pandemia de COVID-19. Dados referentes a confinamento/restrições sociais (uso obrigatório de máscaras faciais e higiene obrigatória das mãos; restrições a viagens internacionais e locais; restrições a visitas familiares e fechamento das escolas) foram coletados de 24 países em cinco continentes. A maioria dos países implantou múltiplos confinamentos, com reabertura parcial ou total. Houve uma redução geral dos casos de tuberculose ativa, tuberculose resistente e tuberculose latente. Embora os confinamentos nacionais tenham sido eficazes na contenção dos casos de COVID-19, vários indicadores de tuberculose foram afetados durante a pandemia.