Relação enfermeiro-pessoa afetada pela Tuberculose fundamentada na teoria do alcance de metas de imogene king / La relación enfermería-Persona afectada por la Tuberculosis, según la Teoría del logro de objetivos de imogene king / The nurse-tuberculosis patient relationship according to Imogene King's theory of goal achievement

Resumo Introdução: As ações desenvolvidas na Atenção Primária à Saúde são um dos pontos fortes de combate à tuberculose. Nesse nível de atenção, o contato contínuo do enfermeiro por meio da consulta de enfermagem permite manter relação com a população adoecida. Diante da relação enfermeiro-pessoa cuidada para o estabelecimento do vínculo e adesão ao tratamento contra tuberculose, compreende-se a importância do referencial teórico de Imogene King para estruturar a interação enfermeiro-pessoa cuidada e oferecer uma dinâmica para esse processo. Objetivo: Analisar a relação enfermeiro-pessoa afetada pela tuberculose fundamentada na Teoria do Alcance de Metas de Imogene King. Método: Estudo descritivo com abordagem qualitativa, com 14 enfermeiros da APS, selecionadas por conveniência. A coleta de dados ocorreu de agosto a novembro de 2018, por meio de entrevista semiestruturada, elaborada com base no Registro Meta-Orientado de Enfermagem de Imogene King. Os dados foram analisados de forme qualitativa pelo Software IRAMUTEQ. A pesquisa foi aprovada pelo Comitê de Ética. Resultados: Após a análise, emergiram quatro classes: 1) relação estabelecida com base no acolhimento; 2) relação enfermeiro-pessoa com tuberculose e o apoio de outros profissionais e familiares; 3) relação estabelecida com vistas ao cumprimento do tratamento; e 4) relação estabelecida para enfrentamento do preconceito diante da tuberculose. Conclusão: O acolhimento, a família e o vínculo entre profissional, paciente e equipe da Atenção Primária à Saúde fortalecem o enfrentamento da doença e reforçam a adesão ao tratamento medicamentoso.

Resumen Introducción: Uno de los puntos fuertes de la lucha contra la tuberculosis son las acciones desarrolladas en la atención primaria de salud. En este nivel asistencial, el contacto continuo de las enfermerías a través de la consulta de enfermería permite mantener una relación con la población enferma. Frente a la relación enfermería-persona para el establecimiento del vínculo y la adherencia al tratamiento contra la tuberculosis, se entiende la importancia del referente teórico de Imogene King para estructurar la interacción enfermería-persona y ofrecer una dinámica para este proceso. Objetivo: Análisis de la relación entre el personal de enfermería y las personas afectadas por la tuberculosis, a partir de la teoría del logro de objetivos de Imogene King. Método: Estudio descriptivo con abordaje cualitativo, con 14 enfermeras de atención primaria de salud, seleccionadas por conveniencia. La recolección de datos ocurrió de agosto a noviembre de 2018, a través de una entrevista semiestructurada, elaborada con base en el registro meta-orientado de enfermería de Imogene King. Los datos fueron analizados cualitativamente utilizando el software IRAMUTEQ. La investigación fue aprobada por el Comité de Ética. Resultados: Después del análisis, surgieron cuatro clases: 1) relación establecida con base en la recepción, 2) relación enfermería-persona con tuberculosis y apoyo de otras personas profesionales y familiares, 3) relación establecida con miras al cumplimiento del tratamiento y 4) relación establecida para combatir los prejuicios contra la tuberculosis. Conclusión: La acogida, la familia y el vínculo entre profesional, paciente y equipo de atención primaria de salud fortalecen el afrontamiento de la enfermedad y refuerzan la adherencia al tratamiento farmacológico.

Abstract Introduction: One of the main aspects in the fight against tuberculosis are the actions developed in Primary Health Care (PHC). At this level of care, the nurse's continuous contact through the nursing consultation allows them to maintain a relationship with the sick population. Regarding the nurse-patient relationship for establishing a bond and the compliance with tuberculosis treatment, we understand the importance of Imogene King's theoretical framework for structuring the nurse-patient interaction and offering a dynamic for this process. Objective: To analyze the nurse-tuberculosis patient relationship based on Imogene King's Theory of Goal Achievement. Method: A descriptive study with a qualitative approach, with 14 PHC nurses, selected by convenience. Data were collected from August to November 2018 through semi-structured interviews based on Imogene King's Meta-Oriented Nursing Record. The data were analyzed qualitatively using the IRAMUTEQ software. The research was approved by the Ethics Committee. Results: After the analysis, four classes emerged: 1) relationship established on the basis of welcoming; 2) nurse-tuberculosis patient relationship and the support of other professionals and family members; 3) relationship established towards treatment compliance; and 4) relationship established to confront prejudice associated with tuberculosis. Conclusion: The welcoming, the family, and the bond between the professional, the patient and Primary Health Care team strengthen the coping with the disease and reinforce the compliance with the pharmacological treatment.

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Determinants of tuberculosis disease development in children in central Ethiopia: A matched case-control study.

BACKGROUND: The risk factors for tuberculosis (TB) disease development in children remained understudied, particularly in low-income countries like Ethiopia. The objective of this study was to identify determinants of TB disease development in general and in relation to BCG vaccination in children in central Ethiopia. METHODS: We employed a 1:1 age-matched case-control design to compare the characteristics of children who developed TB (cases) with those who did not (controls). Data were collected in healthcare facilities in Addis Ababa city, Adama, and Bishoftu towns between September 25, 2021, and June 24, 2022. Two hundred and fifty-six cases were drawn at random from a list of childhood TB patients entered into SPSS software, and 256 controls were selected sequentially at triage from the same healthcare facilities where the cases were treated. A bivariate conditional logistic regression analysis was performed first to select candidate variables with p-values less than or equal to 0.20 for the multivariable model. Finally, variables with a p-value less than 0.05 for a matched adjusted odds ratio (mORadj) were reported as independent determinants of TB disease development. RESULTS: The mean age of the cases was nine years, while that of the controls was 10 years. Males comprised 126 cases (49.2%) and 119 controls (46.5%), with the remainder being females. Ninety-nine (38.7%) of the cases were not BCG-vaccinated, compared to 58 (22.7%) of the controls. Household TB contact was experienced by 43 (16.8%) of the cases and 10 (3.9%) of the controls. Twenty-two (8.6%) of the cases and six (2.3%) of the controls were exposed to a cigarette smoker in their household. Twenty-two (8.6%) of the cases and three (1.2%) of the controls were positive for HIV. Children who were not vaccinated with BCG at birth or within two weeks of birth had more than twice the odds (mORadj = 2.11, 95% CI = 1.28-3.48) of developing TB compared to those who were. Children who ever lived with a TB-sick family member (mORadj = 4.28, 95% CI = 1.95-9.39), smoking family members (mORadj = 3.15, 95% CI = 1.07-9.27), and HIV-infected children (mORadj = 8.71, 95% CI = 1.96-38.66) also had higher odds of developing TB disease than their counterparts. CONCLUSIONS: Being BCG-unvaccinated, having household TB contact, having a smoker in the household, and being HIV-infected were found to be independent determinants of TB disease development among children.

Association of tuberculosis risk with genetic polymorphisms of the immune checkpoint genes PDCD1, CTLA-4, and TIM3.

The immune checkpoint proteins were reported to involve to host resistance to Mycobacteria tuberculosis (Mtb). Here, we evaluated 11 single nucleotide polymorphisms (SNPs) in PDCD1, CTLA4, and HAVCR2 genes between participants with and without TB infection. Genomic DNA isolated from 285 patients with TB and 270 controls without TB infection were used to perform the genotyping assay. Odds ratios were used to characterize the association of 11 SNPs with TB risk. In this study, the various genotypes of the 11 SNPs did not differ significantly in frequency between the non-TB and TB groups. When patients were stratified by sex, however, men differed significantly from women in genotype frequencies at HAVCR2 rs13170556. Odds ratios indicated that rs2227982, rs13170556, rs231775, and rs231779 were sex-specifically associated with TB risk. In addition, the combinations of rs2227982/rs13170556 GA/TC in men and the A-C-C haplotype of rs231775-rs231777-rs231779 in women were significantly associated with TB risk. Our results indicate that rs2227982 in PDCD1 and rs13170556 in HAVCR2 are associated with increased TB susceptibility in men and that the CTLA4 haplotype appears protective against TB in women.

Effectiveness and cost-effectiveness of community-based directly observed treatment (DOT) versus health facility-based DOT of tuberculosis in Africa: protocol for a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO's End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain. OBJECTIVE: To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings. METHODS: We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023443260.

Metabolic changes enhance necroptosis of type 2 diabetes mellitus mice infected with Mycobacterium tuberculosis.

Previously, we found that Mycobacterium tuberculosis (Mtb) infection in type 2 diabetes mellitus (T2DM) mice enhances inflammatory cytokine production which drives pathological immune responses and mortality. In the current study, using a T2DM Mtb infection mice model, we determined the mechanisms that make T2DM mice alveolar macrophages (AMs) more inflammatory upon Mtb infection. Among various cell death pathways, necroptosis is a major pathway involved in inflammatory cytokine production by T2DM mice AMs. Anti-TNFR1 antibody treatment of Mtb-infected AMs from T2DM mice significantly reduced expression of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) (necroptosis markers) and IL-6 production. Metabolic profile comparison of Mtb-infected AMs from T2DM mice and Mtb-infected AMs of nondiabetic control mice indicated that 2-ketohexanoic acid and deoxyadenosine monophosphate were significantly abundant, and acetylcholine and pyridoxine (Vitamin B6) were significantly less abundant in T2DM mice AMs infected with Mtb. 2-Ketohexanoic acid enhanced expression of TNFR1, RIPK3, MLKL and inflammatory cytokine production in the lungs of Mtb-infected nondiabetic mice. In contrast, pyridoxine inhibited RIPK3, MLKL and enhanced expression of Caspase 3 (apoptosis marker) in the lungs of Mtb-infected T2DM mice. Our findings demonstrate that metabolic changes in Mtb-infected T2DM mice enhance TNFR1-mediated necroptosis of AMs, which leads to excess inflammation and lung pathology.

MR1-restricted T cell clonotypes are associated with "resistance" to Mycobacterium tuberculosis infection.

T cells are required for protective immunity against Mycobacterium tuberculosis. We recently described a cohort of Ugandan household contacts of tuberculosis cases who appear to "resist" M. tuberculosis infection (resisters; RSTRs) and showed that these individuals harbor IFN-γ-independent T cell responses to M. tuberculosis-specific peptide antigens. However, T cells also recognize nonprotein antigens via antigen-presenting systems that are independent of genetic background, known as donor-unrestricted T cells (DURTs). We used tetramer staining and flow cytometry to characterize the association between DURTs and "resistance" to M. tuberculosis infection. Peripheral blood frequencies of most DURT subsets were comparable between RSTRs and latently infected controls (LTBIs). However, we observed a 1.65-fold increase in frequency of MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBIs. Single-cell RNA sequencing of 18,251 MR1T cells sorted from 8 donors revealed 5,150 clonotypes that expressed a common transcriptional program, the majority of which were private. Sequencing of the T cell receptor α/T cell receptor δ (TCRα/δ) repertoire revealed several DURT clonotypes were expanded among RSTRs, including 2 MR1T clonotypes that recognized mycobacteria-infected cells in a TCR-dependent manner. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between mycobacteria-reactive MR1T clonotypes and resistance to M. tuberculosis infection.

Burden of COVID-19 pandemic on tuberculosis hospitalisation patterns at a tertiary care hospital in Rajasthan, India: a retrospective analysis.

OBJECTIVE: This study aimed to investigate the burden of the COVID-19 pandemic on tuberculosis (TB) trends, patient demographics, disease types and hospitalisation duration within the Respiratory Medicine Department over three distinct phases: pre-COVID-19, COVID-19 and post-COVID-19. DESIGN: Retrospective analysis using electronic medical records of patients with TB admitted between June 2018 and June 2023 was done to explore the impact of COVID-19 on patients with TB. The study employed a meticulous segmentation into pre-COVID-19, COVID-19 and post-COVID-19 eras. SETTING: National Institute of Medical Science Hospital in Jaipur, Rajasthan, India. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome includes patients admitted to the Respiratory Medicine Department of the hospital and secondary outcome involves the duration of hospital stay. RESULTS: The study encompassed 1845 subjects across the three eras, revealing a reduction in TB incidence during the post-COVID-19 era compared with the pre-COVID-19 period (p<0.01). Substantial demographic shifts were observed, with 5.2% decline in TB incidence among males in the post-COVID-19 era (n=529) compared with the pre-COVID-19 era (n=606). Despite the decrease, overall TB incidence remained significantly higher in males (n=1460) than females (n=385), with consistently elevated rates in rural (65.8%) as compared with the urban areas (34.2%). Extended hospital stays were noted in the post-COVID-19 era compared with the pre-COVID-19 era (p<0.01). CONCLUSION: The study underscores the influence of the COVID-19 pandemic on the TB landscape and hospitalisation dynamics. Notably, patient burden of TB declined during the COVID-19 era, with a decline in the post-COVID-19 era compared with the pre-COVID-19 era. Prolonged hospitalisation in the post-COVID-19 period indicates the need for adaptive healthcare strategies and the formulation of public health policies in a post-pandemic context. These findings contribute to a comprehensive understanding of the evolving TB scenario, emphasising the necessity for tailored healthcare approaches in the aftermath of a global health crisis.

Incidence and risk factors of active tuberculosis among older individuals with latent tuberculosis infection: a cohort study in two high-epidemic sites in eastern China.

Background: The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB. Methods: In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI. Results: In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3). Conclusions: The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.

Serine protease Rv2569c facilitates transmission of Mycobacterium tuberculosis via disrupting the epithelial barrier by cleaving E-cadherin.

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall-associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.

Population structure and spatial distribution of Mycobacterium tuberculosis in Ethiopia.

Ethiopia is one of the countries with a high tuberculosis (TB) burden, yet little is known about the spatial distribution of Mycobacterium tuberculosis (Mtb) lineages. This study identifies the spoligotyping of 1735 archived Mtb isolates from the National Drug Resistance Survey, collected between November 2011 and June 2013, to investigate Mtb population structure and spatial distribution. Spoligotype International Types (SITs) and lineages were retrieved from online databases. The distribution of lineages was evaluated using Fisher's exact test and logistic regression models. The Global Moran's Index and Getis-Ord Gi statistic were utilized to identify hotspot areas. Our results showed that spoligotypes could be interpreted and led to 4 lineages and 283 spoligotype patterns in 91% of the isolates, including 4% of those with multidrug/rifampicin resistance (MDR/RR) TB. The identified Mtb lineages were lineage 1 (1.8%), lineage 3 (25.9%), lineage 4 (70.6%) and lineage 7 (1.6%). The proportion of lineages 3 and 4 varied by regions, with lineage 3 being significantly greater than lineage 4 in reports from Gambella (AOR = 4.37, P < 0.001) and Tigray (AOR = 3.44, P = 0.001) and lineage 4 being significantly higher in Southern Nations Nationalities and Peoples Region (AOR = 1.97, P = 0.026) than lineage 3. Hotspots for lineage 1 were located in eastern Ethiopia, while a lineage 7 hotspot was identified in northern and western Ethiopia. The five prevalent spoligotypes, which were SIT149, SIT53, SIT25, SIT37 and SIT26 account for 42.8% of all isolates under investigation, while SIT149, SIT53 and SIT21 account for 52-57.8% of drug-resistant TB cases. TB and drug resistant TB are mainly caused by lineages 3 and 4, and significant proportions of the prevalent spoligotypes also influence drug-resistant TB and the total TB burden. Regional variations in lineages may result from both local and cross-border spread.

Prediction of tuberculosis clusters in the riverine municipalities of the Brazilian Amazon with machine learning.

OBJECTIVE: Tuberculosis (TB) is the second most deadly infectious disease globally, posing a significant burden in Brazil and its Amazonian region. This study focused on the "riverine municipalities" and hypothesizes the presence of TB clusters in the area. We also aimed to train a machine learning model to differentiate municipalities classified as hot spots vs. non-hot spots using disease surveillance variables as predictors. METHODS: Data regarding the incidence of TB from 2019 to 2022 in the riverine town was collected from the Brazilian Health Ministry Informatics Department. Moran's I was used to assess global spatial autocorrelation, while the Getis-Ord GI* method was employed to detect high and low-incidence clusters. A Random Forest machine-learning model was trained using surveillance variables related to TB cases to predict hot spots among non-hot spot municipalities. RESULTS: Our analysis revealed distinct geographical clusters with high and low TB incidence following a west-to-east distribution pattern. The Random Forest Classification model utilizes six surveillance variables to predict hot vs. non-hot spots. The machine learning model achieved an Area Under the Receiver Operator Curve (AUC-ROC) of 0.81. CONCLUSION: Municipalities with higher percentages of recurrent cases, deaths due to TB, antibiotic regimen changes, percentage of new cases, and cases with smoking history were the best predictors of hot spots. This prediction method can be leveraged to identify the municipalities at the highest risk of being hot spots for the disease, aiding policymakers with an evidenced-based tool to direct resource allocation for disease control in the riverine municipalities.

[Tuberculosis mortality trends and the correlation with the socio-demographic index in Brazil between 2010 and 2019]. / Tendência da mortalidade por tuberculose e relação com o índice sóciodemográfico no Brasil entre 2005-2019.

The scope of this article is to analyze the trend of the standardized mortality rate (SMR) for tuberculosis and its correlation with the developmental status in Brazil. An ecological time series study was conducted to analyze data of deaths from tuberculosis reported between 2005 and 2019 in all states. Data were extracted from the Mortality Information System, the Brazilian Institute of Geography and Statistics, and the Global Burden of Disease study. The temporal trend was analyzed using Prais-Winsten regression. Spearman's correlation analysis between SMR and Socio-Demographic Index (SDI) was also performed. From 2005 to 2019, 68,879 deaths from tuberculosis were recorded in Brazil. The average mortality rate was 2.3 deaths per 100,000 inhabitants. The decreasing trend of SMR due to tuberculosis was observed in Brazil and in all regions. There was a significant negative correlation between SDI and TMP. TMP due to tuberculosis revealed a decreasing trend in Brazil and in all regions. Most states showed a decreasing trend and none of them had an increasing trend. An inverse relationship was found between developmental status and mortality due to tuberculosis.

O objetivo do artigo é analisar a tendência da taxa de mortalidade padronizada (TMP) por tuberculose e sua correlação com o status de desenvolvimento no Brasil. Estudo ecológico de séries temporais que analisou dados de óbitos por tuberculose notificados entre 2005 e 2019 de todos os estados. Os dados foram extraídos do Sistema de Informação sobre Mortalidade, do Instituto Brasileiro de Geografia e Estatística e do estudo da Carga Global de Doenças. A tendência temporal foi analisada pela regressão de Prais-Winsten. A análise da correlação de Spearman entre a TMP e o índice sociodemográfico (socio-demographic index - SDI) também foi realizada. De 2005 a 2019, foram registrados 68.879 óbitos por tuberculose no Brasil. A taxa média de mortalidade foi de 2,3 óbitos por 100.000 habitantes. A tendência decrescente da TMP por tuberculose foi observada no Brasil e em todas as regiões. Verificou-se correlação negativa significativa entre o SDI e a TMP. A maioria dos estados apresentou tendência decrescente e nenhum deles teve tendência crescente. Uma relação inversa foi verificada entre o SDI e a mortalidade por tuberculose.

Factors associated with Community Health Agents' knowledge about tuberculosis.

OBJECTIVE: To analyze the factors associated with the knowledge of Community Health Agents (ACS) about tuberculosis. METHODS: A cross-sectional study was conducted with 110 ACS. A questionnaire was used to assess knowledge about pulmonary tuberculosis (component 1) and the work functions of ACS in the National Tuberculosis Control Program (component 2). The level of knowledge, according to the scores converted into a scale of 0 to 100, was classified as: 0-50% (low), 51-75% (medium), and over 75% (high). Multiple regression was used in the analysis of associated factors. RESULTS: The global score (average of the scores of components 1 and 2) median knowledge was 68.6%. Overall knowledge about tuberculosis was positively associated with the length of professional experience, having received training on tuberculosis, and access to the tuberculosis guide/handbook. CONCLUSIONS: Investments in training and capacity-building strategies for ACS will contribute to increasing these professionals' knowledge, resulting in greater success in tuberculosis control.

Treatment success rate and associated factors among drug susceptible tuberculosis individuals in St. Kizito Hospital, Matany, Napak district, Karamoja region. A retrospective study.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among infectious agents globally. An estimated 10 million people are newly diagnosed and 1.5 million die of the disease annually. Uganda is among the 30 high TB-burdenedd countries, with Karamoja having a significant contribution of the disease incidence in the country. Control of the disease in Karamoja is complex because a majority of the at-risk population remain mobile; partly because of the nomadic lifestyle. This study, therefore, aimed at describing the factors associated with drug-susceptible TB treatment success rate (TSR) in the Karamoja region. METHODS: This was a retrospective study on case notes of all individuals diagnosed with and treated for drug-susceptible TB at St. Kizito Hospital Matany, Napak district, Karamoja from 1st Jan 2020 to 31st December 2021. Data were abstracted using a customised data abstraction tool. Data analyses were done using Stata statistical software, version 15.0. Chi-square test was conducted to compare treatment success rates between years 2020 and 2021, while Modified Poisson regression analysis was performed at multivariable level to determine the factors associated with treatment success. RESULTS: We studied records of 1234 participants whose median age was 31 (IQR: 13-49) years. Children below 15 years of age accounted for 26.2% (n = 323). The overall treatment success rate for the study period was 79.3%(95%CI; 77.0%-81.5%), with a statistically significant variation in 2020 and 2021, 75.4% (422/560) vs 82.4% (557/674) respectively, (P = 0.002). The commonest reported treatment outcome was treatment completion at 52%(n = 647) and death was at 10.4% (n = 129). Older age, undernutrition (Red MUAC), and HIV-positive status were significantly associated with lower treatment success: aPR = 0.87(95%CI; 0.80-0.94), aPR = 0.91 (95%CI; 0.85-0.98) and aPR = 0.88 (95%CI; 0.78-0.98); respectively. Patients who were enrolled in 2021 had a high prevalence of treatment success compared to those enrolled in 2020, aPR = 1.09 (95%CI; 1.03-1.16). CONCLUSION: TB TSR in Matany Hospital was suboptimal. Older age, poor nutrition, and being HIV-positive were negative predictors of treatment success. We propose integrating nutrition and HIV care into TB programming to improve treatment success.

HIV co-infection is associated with reduced Mycobacterium tuberculosis transmissibility in sub-Saharan Africa.

Persons living with HIV are known to be at increased risk of developing tuberculosis (TB) disease upon infection with Mycobacterium tuberculosis (Mtb). However, it has remained unclear how HIV co-infection affects subsequent Mtb transmission from these patients. Here, we customized a Bayesian phylodynamic framework to estimate the effects of HIV co-infection on the Mtb transmission dynamics from sequence data. We applied our model to four Mtb genomic datasets collected in sub-Saharan African countries with a generalized HIV epidemic. Our results confirm that HIV co-infection is a strong risk factor for developing active TB. Additionally, we demonstrate that HIV co-infection is associated with a reduced effective reproductive number for TB. Stratifying the population by CD4+ T-cell count yielded similar results, suggesting that, in this context, CD4+ T-cell count is not a better predictor of Mtb transmissibility than HIV infection status alone. Together, our genome-based analyses complement observational household contact studies, and more firmly establish the negative association between HIV co-infection and Mtb transmissibility.

Systematic review and meta-analysis of Tuberculosis and COVID-19 Co-infection: Prevalence, fatality, and treatment considerations.

BACKGROUND: Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. METHODS: This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. RESULTS: From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18-3.68) for TB-COVID patients versus single COVID patients. CONCLUSION: TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection.

Mortality among extrapulmonary tuberculosis patients in the HIV endemic setting: lessons from a tertiary level hospital in Mbeya, Tanzania.

Extrapulmonary tuberculosis (EPTB) has received less attention than pulmonary tuberculosis due to its non-contagious nature. EPTB can affect any organ and is more prevalent in people living with HIV. Low- and middle-income countries are now facing the double burden of non-communicable diseases (NCDs) and HIV, complicating the management of patients with symptoms that could be compatible with both EPTB and NCDs. Little is known about the risk of death of patients presenting with symptoms compatible with EPTB. We included patients with a clinical suspicion of EPTB from a tertiary level hospital in Mbeya, Tanzania, to assess their risk of dying. A total of 113 (61%) patients were classified as having EPTB, and 72 (39%) as having non-TB, with corresponding mortality rates of 40% and 41%. Associated factors for mortality in the TB groups was hospitalization and male sex. Risk factors for hospitalization was having disease manifestation at any site other than lymph nodes, and comorbidities. Our results imply that NCDs serve as significant comorbidities amplifying the mortality risk in EPTB. To strive towards universal health coverage, focus should be on building robust health systems that can tackle both infectious diseases, such as EPTB, and NCDs.

Exploring optimal drug targets through subtractive proteomics analysis and pangenomic insights for tailored drug design in tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, ranks among the top causes of global human mortality, as reported by the World Health Organization's 2022 TB report. The prevalence of M. tuberculosis strains that are multiple and extensive-drug resistant represents a significant barrier to TB eradication. Fortunately, having many completely sequenced M. tuberculosis genomes available has made it possible to investigate the species pangenome, conduct a pan-phylogenetic investigation, and find potential new drug targets. The 442 complete genome dataset was used to estimate the pangenome of M. tuberculosis. This study involved phylogenomic classification and in-depth analyses. Sequential filters were applied to the conserved core genome containing 2754 proteins. These filters assessed non-human homology, virulence, essentiality, physiochemical properties, and pathway analysis. Through these intensive filtering approaches, promising broad-spectrum therapeutic targets were identified. These targets were docked with FDA-approved compounds readily available on the ZINC database. Selected highly ranked ligands with inhibitory potential include dihydroergotamine and abiraterone acetate. The effectiveness of the ligands has been supported by molecular dynamics simulation of the ligand-protein complexes, instilling optimism that the identified lead compounds may serve as a robust basis for the development of safe and efficient drugs for TB treatment, subject to further lead optimization and subsequent experimental validation.

Targeting Mycobacterium tuberculosis pH-driven adaptation.

Mycobacterium tuberculosis (Mtb) senses and adapts to host environmental cues as part of its pathogenesis. One important cue sensed by Mtb is the acidic pH of its host niche - the macrophage. Acidic pH induces widespread transcriptional and metabolic remodelling in Mtb. These adaptations to acidic pH can lead Mtb to slow its growth and promote pathogenesis and antibiotic tolerance. Mutants defective in pH-dependent adaptations exhibit reduced virulence in macrophages and animal infection models, suggesting that chemically targeting these pH-dependent pathways may have therapeutic potential. In this review, we discuss mechanisms by which Mtb regulates its growth and metabolism at acidic pH. Additionally, we consider the therapeutic potential of disrupting pH-driven adaptations in Mtb and review the growing class of compounds that exhibit pH-dependent activity or target pathways important for adaptation to acidic pH.