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Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
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Antituberculosos , Nitroimidazóis , Oxazóis , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Humanos , Masculino , Feminino , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Estudos Prospectivos , Rifampina/efeitos adversos , Pessoa de Meia-Idade , Oxazóis/efeitos adversos , Oxazóis/uso terapêutico , Oxazóis/administração & dosagem , Antituberculosos/efeitos adversos , Tuberculose Pulmonar/tratamento farmacológico , Nitroimidazóis/efeitos adversos , Nitroimidazóis/uso terapêutico , Nitroimidazóis/administração & dosagem , Idoso , China , Adulto Jovem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologiaRESUMO
This retrospective cohort study identified factors associated with loss of follow-up and death due to tuberculosis (TB) in the homeless population (HP) in Brazil, estimating odds ratios (OR) and their 95% confidence intervals (95%CI) by multinomial logistic regression. A total of 3,831 TB cases in this population were analyzed, of which 57.0% had unfavorable outcomes. Loss of follow-up was associated with: history of abandonment (OR=2.38; 95%CI 2.05-2.77), unknown HIV serology (OR=1.79; 95%CI 1.38-2.32), HIV coinfection (OR=1.73; 95%CI 1.46-2.06), drug use (OR=1.54; 95%CI 1.31-1.80), age (OR=0.98; 95%CI 0.97-0.99), mixed clinical form (OR=0.64; 95%CI 0.42-0.97), extrapulmonary form (OR=0.46; 95%CI 0.29-0.73), government beneficiary (OR=0.64; 95%CI 0.50-0.81), and supervised treatment (OR=0.52; 95%CI 0.45-0.60). Regarding death, the following were associated: age (OR=1.03; 95%CI 1.01-1.05), unknown HIV serology (OR=2.39; 95%CI 1.48-3.86), alcohol consumption (OR=1.81; 95%CI 1.27-2.58), and supervised treatment (OR=0.70; 95%CI 0.51-0.96). Overlapping vulnerabilities in the health-disease process of homeless individuals with TB were observed, requiring comprehensive and cross-sectoral care practices.
Esta coorte retrospectiva identificou os fatores associados à perda de seguimento e ao óbito por tuberculose na população em situação de rua no Brasil, estimando-se as odds ratios (OR) e seus intervalos de confiança de 95% (IC95%) por regressão logística multinominal. Analisaram-se 3.831 casos de tuberculose nessa população, dos quais 57,0% tiveram desfechos desfavoráveis. Associaram-se à perda de seguimento: histórico de abandono (OR=2,38; IC95% 2,05-2,77), desconhecimento da sorologia do HIV (OR=1,79; IC95% 1,38-2,32) e coinfecção com HIV (OR=1,73; IC95% 1,46-2,06), uso de drogas (OR=1,54; IC95% 1,31-1,80), idade (OR=0,98; IC95% 0,97-0,99), forma clínica mista (OR=0,64; IC95% 0,42-0,97) e extrapulmonar (OR=0,46; IC95% 0,29-0,73), auxílio de programa governamental (OR=0,64; IC95% 0,50-0,81) e tratamento supervisionado (OR=0,52; IC95% 0,45-0,60). Em relação ao óbito, associaram-se: idade (OR=1,03; IC95% 1,01-1,05), desconhecimento da sorologia do HIV (OR=2,39; IC95% 1,48-3,86), uso de álcool (OR=1,81; IC95% 1,27-2,58) e tratamento supervisionado (OR=0,70; IC95% 0,51-0,96). Percebeu-se a sobreposição de vulnerabilidades no processo saúde-doença das pessoas em situação de rua com tuberculose, demandando práticas cuidativas intersetoriais e integrais.
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Pessoas Mal Alojadas , Perda de Seguimento , Tuberculose , Humanos , Pessoas Mal Alojadas/estatística & dados numéricos , Estudos Retrospectivos , Brasil/epidemiologia , Masculino , Feminino , Adulto , Tuberculose/mortalidade , Tuberculose/epidemiologia , Pessoa de Meia-Idade , Estudos de Coortes , Adulto Jovem , SeguimentosRESUMO
This work was a descriptive study that analyzed the performance of health services in 112 municipalities (g100) characterized by more than 80,000 inhabitants, low public revenue, and socioeconomic vulnerability. Based on the Projeto de Avaliação de Desempenho do Sistema de Saúde, 31 indicators of funding, resources, access, effectiveness, acceptability, and appropriateness were selected for the period of 2017-2020, and were compared to the variations of each year's indicators year on year. In 2020, an increase in funding, especially SUS transfers (31.6%), was observed. The availability of hospital beds had been decreasing between 2017 and 2019, but began to increase again in 2020; likewise, the availability of health professionals also showed a slight increase. A decline was observed in cervical and breast cancer screening exams of nearly 40% (2020), as well as a decrease in surgical procedures, such as cataracts and angioplasties. The hospitalizations due to conditions manageable by primary care were 15.8% in 2020, 14.1% lower than in 2019. A 55.8% increase in mortality due to diabetes and greater tuberculosis treatment non-adherence was also observed. The pandemic context calls for caution when interpreting results, which highlight access barriers and postponements of proper health care.
Estudo descritivo que analisou o desempenho dos serviços de saúde de um grupo de 112 municípios denominado g100 caracterizado por mais de 80 mil habitantes, baixa receita pública e vulnerabilidade socioeconômica. Do Projeto de Avaliação de Desempenho do Sistema de Saúde, foram selecionados 31 indicadores de financiamento, recursos, acesso, efetividade, aceitabilidade e adequação, para o período 2017-2020, e comparadas variações de cada ano em relação ao anterior. Em 2020, houve aumento no aporte financeiro, especialmente por transferências SUS (31,6%). A disponibilidade de leitos vinha decaindo entre 2017 e 2019, aumentou em 2020 e a oferta de profissionais de saúde apresentou leve aumento. Houve redução nos exames de rastreamento de câncer de colo do útero e mama de quase 40% (2020), e reduções de internações cirúrgicas, como cataratas e angioplastias. O percentual de internações por condições sensíveis à atenção primária foi 15,8% em 2020, 14,1% menor do que em 2019. Houve aumento de 55,8% na mortalidade por diabetes e maior abandono do tratamento de tuberculose. O contexto pandêmico exige cautela na interpretação de resultados, que apontam para barreiras de acesso e postergação na prestação de cuidados.
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Acessibilidade aos Serviços de Saúde , Populações Vulneráveis , Humanos , Brasil , Cidades , Atenção à Saúde/organização & administração , Fatores Socioeconômicos , Hospitalização/estatística & dados numéricos , Programas Nacionais de Saúde/organização & administração , Serviços de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricosRESUMO
OBJECTIVE: To evaluate the auxiliary diagnostic value of T cells spot test of Mycobacterium tuberculosis infection (T-SPOT.TB) for pulmonary and extra-pulmonary tuberculosis among the elderly. METHODS: A total of 173 elderly patients at ages of 60 years and older and with suspected tuberculosis that were admitted to People's Hospital of Xinjiang Uygur Autonomous Region during the period from October 2022 through February 2024 were enrolled, and all patients underwent T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests. The etiological tests of MTB served as a gold standard, and the diagnostic values of T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests for pulmonary and extra-pulmonary tuberculosis were compared among the elderly patients. RESULTS: Of the 173 elderly patients suspected of tuberculosis, there were 44 patients definitely diagnosed with pulmonary tuberculosis, 30 cases with extra-pulmonary tuberculosis, and 99 cases without tuberculosis. The sensitivities of T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests were 86.5%, 27.0% and 54.1% for diagnosis of tuberculosis. The sensitivities of T-SPOT.TB were 86.4% and 86.7% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with an 80.8% specificity for diagnosis of tuberculosis. The sensitivities of GeneXpert MTB/RIF were 56.8% and 50.0% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with a 100.0% specificity each, and the sensitivities of acid fast staining were 31.8% and 20.0% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with a 100.0% specificity each. In addition, the areas under the receiver operating characteristic curve were 0.836, 0.635 and 0.770 for diagnosis of tuberculosis with T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests among the elderly patients, respectively. CONCLUSIONS: T-SPOT.TB has a high auxiliary diagnostic value for both pulmonary and extra-pulmonary tuberculosis among elderly patients.
Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Idoso , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/fisiologia , Masculino , Feminino , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/imunologia , Pessoa de Meia-Idade , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose/imunologia , Idoso de 80 Anos ou mais , Linfócitos T/imunologia , Sensibilidade e Especificidade , Tuberculose ExtrapulmonarRESUMO
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4th month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
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Antituberculosos , Epididimo , Imunocompetência , Imageamento por Ressonância Magnética , Tuberculose dos Genitais Masculinos , Humanos , Masculino , Adulto Jovem , Antituberculosos/administração & dosagem , Epididimo/patologia , Epididimo/microbiologia , Tuberculose dos Genitais Masculinos/diagnóstico , Tuberculose dos Genitais Masculinos/tratamento farmacológico , Orquiectomia , Convulsões/etiologia , Anticonvulsivantes/administração & dosagem , Tuberculoma Intracraniano/diagnóstico , Tuberculoma Intracraniano/tratamento farmacológicoRESUMO
Introduction: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease. Methods: To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa. Results: Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1. Discussion: Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.
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Infecções por HIV , Imunofenotipagem , Neutrófilos , Tuberculose Pulmonar , Humanos , Neutrófilos/imunologia , Masculino , Adulto , Feminino , Infecções por HIV/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia , África do Sul , Coinfecção/imunologia , Pessoa de Meia-Idade , Fenótipo , Citometria de Fluxo , Adulto Jovem , Mycobacterium tuberculosis/imunologiaRESUMO
Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Emirados Árabes Unidos/epidemiologia , Humanos , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Feminino , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Pessoa de Meia-Idade , Farmacorresistência Bacteriana , Adolescente , Testes de Sensibilidade Microbiana , Adulto Jovem , Vigilância da PopulaçãoRESUMO
Background: We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic. Methods: TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic. Results: A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%). Conclusion: The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic.
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COVID-19 , Tuberculose , Humanos , COVID-19/mortalidade , Feminino , Pessoa de Meia-Idade , Masculino , Estados Unidos/epidemiologia , Adulto , Idoso , Tuberculose/mortalidade , Fatores Sexuais , Idoso de 80 Anos ou mais , PandemiasRESUMO
The occurrence of transient culture positivity for Mycobacterium tuberculosis (MTB), known as mirage de tuberculose, poses significant challenges in understanding its spectrum and implications. Here, we report a case of transient culture positivity, oscillating between detectable and non-detectable MTB cultures with minimal radiological features and review the literature on this phenomenon. The scarcity of scientific literature on this subject stems from the inherent impossibility of systematically studying mirage de tuberculose. Ethical and public health concerns prevent withholding treatment to monitor spontaneous reversion to negative cultures. Based on the literature, we estimate that mirage de tuberculose occurs in approximately one-third of individuals infected with MTB who exhibit no symptoms. Despite the inherently limited nature of these findings, they suggest that the significance of mirage de tuberculose may be greater than currently perceived. Managing cases of mirage de tuberculose presents formidable challenges from a public health perspective. Striking a balance between prompt treatment initiation to prevent transmission and the risk of unnecessary treatment requires careful consideration. In conclusion, mirage de tuberculose remains a poorly understood clinical entity with very limited literature available. Advancing research and interdisciplinary collaborations are essential to unravel the intricacies of this phenomenon and develop effective strategies to address its public health challenges.
L'apparition d'une culture transitoire positive pour Mycobacterium tuberculosis (MTB), connue sous le nom de mirage de tuberculose, pose des défis importants dans la compréhension de son spectre et de ses implications. Nous rapportons ici un cas de positivité transitoire des cultures, oscillant entre des cultures MTB détectables et non détectables avec des caractéristiques radiologiques minimales et passons en revue la littérature sur ce phénomène. La rareté de la littérature scientifique sur ce sujet provient de l'impossibilité inhérente d'étudier systématiquement le mirage de tuberculose. Des préoccupations éthiques et de santé publique empêchent l'interruption du traitement pour surveiller le retour spontané à des cultures négatives. Sur la base de la littérature, nous estimons que le mirage de tuberculose survient chez environ un tiers des personnes infectées par le MTB qui ne présentent aucun symptôme. Malgré la nature intrinsèquement limitée de ces résultats, ils suggèrent que l'importance du mirage de tuberculose pourrait être plus grande que ce que l'on perçoit actuellement. La prise en charge des mirages de tuberculose présente des défis considérables du point de vue de la santé publique. Il faut trouver un équilibre entre l'instauration rapide du traitement pour prévenir la transmission et le risque d'un traitement inutile. En conclusion, le mirage de tuberculose reste une entité clinique mal comprise et la littérature disponible est très limitée. L'avancement de la recherche et les collaborations interdisciplinaires sont essentiels pour démêler les subtilités de ce phénomène et élaborer des stratégies efficaces pour relever ses défis en matière de santé publique.
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OBJECTIVES: To measure the progress towards reducing TB-related catastrophic costs in 19 zones of Amhara, Oromia, SNNP (Southern Nations and Nationalities, and Peoples) and Sidama Regions of Ethiopia. METHODS: A baseline survey was conducted in randomly selected health facilities from all districts within the 19 zones from November 2020 to February 2021. Interventions targeting the major drivers of catastrophic costs identified in the baseline survey, such as installation of 126 GeneXpert and 13 Truenat machines, securing connectivity of 372 GeneXpert, establishing alternative specimen referral systems, and capacity-building of health workers, were implemented. A follow-up survey was conducted from October to December 2022. The WHO generic tool was used to collect data based on probability proportional to size. Data were entered into STATA software, and the proportion of catastrophic costs was calculated and compared between the two surveys. RESULTS: A total of 433 and 397 patients participated in the baseline and follow-up surveys, respectively. The proportion of catastrophic costs reduced from 64.7% to 43.8% (P < 0.0001). The share of direct non-medical costs decreased from 76.2% to 19.2%, while medical and indirect costs increased from 11.6% and 12.3% to 30.4% and 52.4 %. CONCLUSION: The proportion of households facing TB-related catastrophic costs has significantly reduced over the 2-year period. However, it remains unacceptably high and varies among regions. Further reducing the catastrophic costs requires multisectoral response, reviewing the TB service exemption policy, further decentralisation and improving the quality of TB services.
OBJECTIFS: Mesurer les progrès accomplis dans la réduction des coûts catastrophiques liés à la TB dans 19 zones des régions d'Amhara, d'Oromia, de SNNP (Région des nations, nationalités et peuples du Sud) et de Sidama en Éthiopie. MÉTHODES: Une enquête de base a été menée dans des établissements de santé sélectionnés au hasard dans tous les districts des 19 zones de novembre 2020 à février 2021. Des interventions ciblant les principaux facteurs de coûts catastrophiques identifiés dans l'enquête de référence, telles que l'installation de 126 machines GeneXpert et 13 Truenat, la sécurisation de la connectivité de 372 GeneXpert, la mise en place de systèmes alternatifs d'orientation des échantillons et le renforcement des capacités des agents de santé, ont été mises en Åuvre. Une enquête de suivi a été menée d'octobre à décembre 2022. L'outil générique de l'OMS a été utilisé pour recueillir des données fondées sur une probabilité proportionnelle à la taille. Les données ont été saisies dans le logiciel STATA, et la proportion des coûts catastrophiques a été calculée et comparée entre les deux enquêtes. RÉSULTATS: Au total, 433 et 397 patients ont participé respectivement à l'enquête de base et à l'enquête de suivi. La proportion des coûts catastrophiques est passée de 64,7% à 43,8% (P < 0,0001). La part des coûts non médicaux directs a diminué, passant de 76,2% à 19,2%, tandis que les coûts médicaux et indirects sont passés de 11,6% et 12,3% à 30,4% et 52,4%. CONCLUSION: La proportion de ménages confrontés à des coûts catastrophiques liés à la tuberculose a considérablement diminué au cours de la période de 2 ans. Cependant, il reste inacceptable et varie selon les régions. Pour réduire davantage les coûts catastrophiques, il faut une réponse multisectorielle, une révision de la politique d'exemption des services de lutte contre la TB, une décentralisation plus poussée et une amélioration de la qualité des services de lutte contre la TB.
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Background: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB. Methods: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed. Results: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination. Conclusion: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.
Assuntos
Antígenos CD , Linfócitos T CD8-Positivos , Proteína do Gene 3 de Ativação de Linfócitos , Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/genética , Linfócitos T CD8-Positivos/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Animais , Antígenos CD/genética , Vacina BCG/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Interleucina-2/metabolismo , Interleucina-2/genética , Perfilação da Expressão Gênica , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Interleucina-12/genética , Interleucina-12/metabolismo , Perforina/genética , Perforina/metabolismo , MasculinoRESUMO
Tuberculosis is one of the oldest known diseases and it remains one of the main causes of morbidity and mortality, especially in developing countries. It is associated with social inequalities and affects different age groups. Tuberculosis in children and adolescents should be considered a sentinel event, since it is linked to a recent infection through contact with bacilliferous adults. We report an immunocompetent 15-year-old adolescent with tuberculosis, exhibiting pulmonary, osteoarticular, and cutaneous involvement. Conventional treatment with tuberculostatic drugs for a year had satisfactory results without sequelae.
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Antituberculosos , Imunocompetência , Humanos , Adolescente , Antituberculosos/uso terapêutico , Masculino , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/patologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Osteoarticular/tratamento farmacológico , Tuberculose Osteoarticular/diagnósticoAssuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/administração & dosagem , Antituberculosos/farmacologia , Tuberculose/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificaçãoRESUMO
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Programas de Rastreamento , Tuberculose Pulmonar , Humanos , Índia/epidemiologia , Estudos Transversais , Prevalência , Adulto , Masculino , Feminino , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/diagnóstico , Pessoa de Meia-Idade , Programas de Rastreamento/métodos , Adulto Jovem , Adolescente , Radiografia Torácica , Criança , Idoso , Pré-EscolarRESUMO
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Agentes Comunitários de Saúde , Farmácias , Tuberculose , Humanos , Masculino , Feminino , Estudos Transversais , Agentes Comunitários de Saúde/organização & administração , Adulto , Uganda , Pessoa de Meia-Idade , Tuberculose/tratamento farmacológico , Tuberculose/diagnóstico , Acessibilidade aos Serviços de Saúde , Setor Privado , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
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Antituberculosos , Tuberculose Ocular , Humanos , Austrália Ocidental/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Antituberculosos/administração & dosagem , Tuberculose Ocular/tratamento farmacológico , Tuberculose Ocular/diagnóstico , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Resultado do Tratamento , Adolescente , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/tratamento farmacológico , SeguimentosRESUMO
Assuntos
Tuberculose , Humanos , Taiwan/epidemiologia , Masculino , Tuberculose/epidemiologia , Tuberculose/tratamento farmacológico , Notificação de Doenças/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Sistema de Registros , Adolescente , Programas Nacionais de Saúde , Criança , Pré-Escolar , Bases de Dados Factuais , LactenteRESUMO
Despite its historical decline, TB remains a significant cause of infectious disease-related global deaths. The lack of reliable diagnostic tests for vulnerable groups, such as children and immunocompromised patients, remains a challenge for TB control. For decades, it has been recognised that exhaled breath has great potential as a non-invasive and universally accessible clinical alternative to sputum and invasive sampling methods. Although translation into clinical practice has not yet occurred, there has been significant progress with promising results in various applications, including diagnosis, estimation of infectiousness, and monitoring of treatment response. More recently, the COVID-19 pandemic reignited global interest in this field and technological advances have further accelerated its development. In the coming decade, breath sampling will enhance our understanding of respiratory infectious diseases and host-immune responses, which may lead to clinical applications. Here we discuss the diagnostic landscape of TB and the current state of the art of breath sampling.
Assuntos
Testes Respiratórios , COVID-19 , Tuberculose Pulmonar , Humanos , Testes Respiratórios/métodos , Tuberculose Pulmonar/diagnóstico , COVID-19/diagnóstico , Expiração , SARS-CoV-2RESUMO
Using ultrasound findings and clinical characteristics, we constructed and validated a new nomogram for distinguishing epididymal tuberculosis from nontuberculous epididymitis, both of which share similar symptoms. We retrospectively examined data of patients with epididymal tuberculosis and nontuberculous epididymitis hospitalized between January 1, 2013, and March 31, 2023. Eligible patients were randomly assigned to derivation and validation cohorts (ratio, 7:3). We drew a nomogram to construct a diagnostic model through multivariate logistic regression and visualize the model. We used concordance index, calibration plots, and decision curve analysis to assess the discrimination, calibration, and clinical usefulness of the nomogram, respectively. In this study, 136 participants had epididymal tuberculosis and 79 had nontuberculous epididymitis. Five variables-C-reactive protein level, elevated scrotal skin temperature, nodular lesion, chronic infection, and scrotal skin ulceration-were significant and used to construct the nomogram. Concordance indices of the derivation and validation cohorts were 0.95 and 0.96, respectively (95% confidence intervals, 0.91-0.98 and 0.92-1.00, respectively). Decision curve analysis of this nomogram revealed that it helped differentiate epididymal tuberculosis from nontuberculous epididymitis. This nomogram may help clinicians distinguish between epididymal tuberculosis and nontuberculous epididymitis, thereby increasing diagnosis accuracy.