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.

New insight into arginine and tryptophan metabolism in macrophage activation during tuberculosis.

Arginine and tryptophan are pivotal in orchestrating cytokine-driven macrophage polarization and immune activation. Specifically, interferon-gamma (IFN-γ) stimulates inducible nitric oxide synthase (iNOS) expression), leading to the conversion of arginine into citrulline and nitric oxide (NO), while Interleukin-4 (IL4) promotes arginase activation, shifting arginine metabolism toward ornithine. Concomitantly, IFN-γ triggers indoleamine 2,3-dioxygenase 1 (IDO1) and Interleukin-4 induced 1 (IL4i1), resulting in the conversion of tryptophan into kynurenine and indole-3-pyruvic acid. These metabolic pathways are tightly regulated by NAD+-dependent sirtuin proteins, with Sirt2 and Sirt5 playing integral roles. In this review, we present novel insights that augment our understanding of the metabolic pathways of arginine and tryptophan following Mycobacterium tuberculosis infection, particularly their relevance in macrophage responses. Additionally, we discuss arginine methylation and demethylation and the role of Sirt2 and Sirt5 in regulating tryptophan metabolism and arginine metabolism, potentially driving macrophage polarization.

Photoelectrochemical sensing of isoniazid and streptomycin based on metal Bi-doped BiOI microspheres grown on book-shape layers of Ti3C2 heterostructures.

Isoniazid and streptomycin are vital drugs for treating tuberculosis, which are utilized as efficient anti-tuberculosis agents. This paper presents a novel visible-light-driven composite photocatalyst Ti3C2/Bi/BiOI, which was built from Ti3C2 nanosheets and Bi/BiOI microspheres. Photoelectrochemical (PEC) sensors based on Ti3C2/Bi/BiOI were synthesized for isoniazid identification, which showed a linear concentration range of 0.1-125 µM with a detection limit of 0.05 µM (S/N = 3). Moreover, we designed a PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI to detect streptomycin in 0.1 M PBS covering the electron donor isoniazid, because the isoniazid consumes photogenerated holes thus increasing the photocurrent effectively and preventing photogenerated electron-hole pairs from being recombined. Furthermore, PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI were synthesized for streptomycin identification, which exhibited a linear concentration range of 0.01-1000 nM with a detection limit of 2.3 × 10-3 nM (S/N = 3), and are well stable in streptomycin sensing.

Identification of hub genes and establishment of a diagnostic model in tuberculosis infection.

Tuberculosis (TB) poses significant challenges due to its high transmissibility within populations and intrinsic resistance to treatment, rendering it a formidable respiratory disease with a substantial susceptibility burden. This study was designed to identify new potential therapeutic targets for TB and establish a diagnostic model. mRNA expression data for TB were from GEO database, followed by conducting differential expression analysis. The top 50 genes with differential expression were subjected to GO and KEGG enrichment analyses. To establish a PPI network, the STRING database was utilized, and hub genes were identified utilizing five algorithms (EPC, MCC, MNC, Radiality, and Stress) within the cytoHubba plugin of Cytoscape software. Furthermore, a hub gene co-expression network was constructed using the GeneMANIA database. Consistency clustering was performed on hub genes, and ssGSEA was utilized to analyze the extent of immune infiltration in different subgroups. LASSO analysis was employed to construct a diagnostic model, and ROC curves were used for validation. Through the analysis of GEO data, a total of 159 genes were identified as differentially expressed. Further, GO and KEGG enrichment analyses revealed that these genes were mainly enriched in viral defense, symbiotic defense, and innate immune response-related pathways. Hub genes, including DDX58, IFIT2, IFIH1, RSAD2, IFI44L, OAS2, OAS1, OASL, IFIT1, IFIT3, MX1, STAT1, and ISG15, were identified using cytoHubba analysis of the PPI network. The GeneMANIA analysis unmasked that the co-expression rate of hub genes was 81.55%, and the physical interaction rate was 12.27%. Consistency clustering divided TB patients into two subgroups, and ssGSEA revealed different degrees of immune infiltration in different subgroups. LASSO analysis identified IFIT1, IFIT2, IFIT3, IFIH1, RSAD2, OAS1, OAS2, and STAT1 as eight immune-related key genes, and a diagnostic model was constructed. The ROC curve demonstrated that the model exhibited excellent diagnostic performance. DDX58, IFIT2, IFIH1, RSAD2, IFI44L, OAS2, OAS1, OASL, IFIT1, IFIT3, MX1, STAT1, and ISG15 were hub genes in TB, and the diagnostic model based on eight immune-related key genes exhibited good diagnostic performance.

Deaths among Women of Reproductive Age: an Explorative Case Study among Abortion Seekers.

In Nepal, abortion was legalized in 2002. Yet many women are denied abortion services. Women denied abortion services may either continue their pregnancies or find abortion care elsewhere. However, what is not known is the consequences on women, and their children after accessing abortion services or after being denied abortion services. This comment aims to understand the cause of death of women who sought abortion services between 2019 and 2020 and were enrolled in a longitudinal nationwide study of the consequences of legal abortion access in Nepal. Women were interviewed 6 weeks and every 6 months for 3 years after seeking abortion. During the follow-up interviews, the field research assistants were informed about the death of the clients. Once the death was reported, a trained senior research staff visited the deceased persons house and interviewed family members including husbands, maternal parents or in-laws to explore the cause of death. A total of nine deaths were reported between April 2019 and December 2022. Out of nine deceased women, four received abortions while five of them were initially denial abortion services. The majority of the deaths were due to suicide followed by tuberculosis. None of the deaths were caused by abortion or birth. Keywords: Death; Nepal; reproductive ages; womens health.

Tuberculosis Chest X-Ray Image Retrieval System Using Deep Learning Based Biomarker Predictions.

The world health organization's global tuberculosis (TB) report for 2022 identifies TB, with an estimated 1.6 million, as a leading cause of death. The number of new cases has risen since 2020, particularly the number of new drug-resistant cases, estimated at 450,000 in 2021. This is concerning, as treatment of patients with drug resistant TB is complex and may not always be successful. The NIAID TB Portals program is an international consortium with a primary focus on patient centric data collection and analysis for drug resistant TB. The data includes images, their associated radiological findings, clinical records, and socioeconomic information. This work describes a TB Portals' Chest X-ray based image retrieval system which enables precision medicine. An input image is used to retrieve similar images and the associated patient specific information, thus facilitating inspection of outcomes and treatment regimens from comparable patients. Image similarity is defined using clinically relevant biomarkers: gender, age, body mass index (BMI), and the percentage of lung affected per sextant. The biomarkers are predicted using variations of the DenseNet169 convolutional neural network. A multi-task approach is used to predict gender, age and BMI incorporating transfer learning from an initial training on the NIH Clinical Center CXR dataset to the TB portals dataset. The resulting gender AUC, age and BMI mean absolute errors were 0.9854, 4.03years and 1.67kgm2. For the percentage of sextant affected by lesions the mean absolute errors ranged between 7% to 12% with higher error values in the middle and upper sextants which exhibit more variability than the lower sextants. The retrieval system is currently available from https://rap.tbportals.niaid.nih.gov/find_similar_cxr.

Comprehension of Calcitriol Levels in Pregnant Women With Latent Tuberculosis and Immune Function in their Newborns.

Background: Pregnant women with latent tuberculosis infection (LTBI) may develop active tuberculosis infection and could infect their neonates, which could impair the child's immune system due to infection-mediated immunological responses. In order to develop a preventative TB program in this study, we desired to understand the impact of calcitriol in LTBI pregnant women and immunological responses in neonates. Patients and Methods: In three hospitals in Medan, North Sumatra, we implemented a case-control design with 84 pregnant women in their third trimester and their newborns. We determined the levels of calcitriol, cathelicidin, and interferon gamma (IFN-γ) in women between December 2021 and July 2022. These measurements were then compared to the newborns' levels of calcitriol, cathelicidin, IFN-γ, and Toll-Like Receptor (TLR) 2. Analyses were performed using the Chi-squared and Fisher's tests, while Spearman correlations were employed to assess for correlations. Results: 42 pregnant women with LTBI (interferon gamma release assay (IGRA) positive) and 42 pregnant women without LTBI (IGRA negative) participated in the study. The findings demonstrated that pregnant women with LTBI were at increased risk for calcitriol deficiency (Odds Ratio (OR) = 3.667, p = 0.006), which had an impact on the calcitriol levels of their unborn children (p = 0.038). TLR2 levels and calcitriol levels were substantially associated with LTBI pregnant women and their healthy neonates (p = 0.048; p = 0.005). Cathelicidin levels in the newborns of non-LTBI pregnant women were influenced by their higher calcitriol levels (p = 0.043). Pregnant women with LTBI had higher levels of cathelicidin and IFN-γ than those without it (p = 0.03; p = 0.001). Conclusion: Pregnant LTBI women's calcitriol levels had an impact on the calcitriol levels of their newborns. Mother's immunological responses and babies' calcitriol levels affected the levels of cathelicidin, IFN-γ, and TLR2 in newborns.

Dancing Out of Step: A Case of Tuberculous Meningitis Presenting as Childhood Chorea.

Background: Acute to subacute pediatric movement disorders require prompt diagnosis to identify potentially treatable diseases. Case Report: We present a 6-year-old male with a three-week history of generalized chorea transitioning to predominantly right-sided hemichorea and then to left hemiplegia. Discussion: We review the mechanisms in tuberculous meningitis underlying his movement abnormalities.

Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India.

Background: World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. Methods: Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months. Results: Of 17 patients, median age was 23 years (IQR = 21-30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. Conclusion: Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Monocytes predict prognosis and successful treatment in older patients with miliary tuberculosis.

Background: The increasing number of patients with miliary tuberculosis (MTB) is a concern in an aging society because of its high mortality rate. Several prognostic biomarkers for MTB have been identified; however, the predictive ability of monocytes as biomarkers remains unknown. This study demonstrates the usefulness of monocytes as prognostic biomarkers for MTB. Materials and methods: We retrospectively compared the clinical findings of 52 patients with MTB hospitalized between April 2013 and October 2021. The predictive ability of biomarkers for 3-month prognosis and their cutoff values were calculated. Survival times and longitudinal changes in monocytes after initiating treatment were compared. Results: A smaller number of monocytes (#M), higher lymphocyte-monocyte ratio (LMR), higher neutrophil-monocyte ratio, and poorer performance status were associated with death within 3 months. #M was an independent prognostic factor. #M and LMR exhibited the highest predictive performance compared to others using receiver operating characteristic curve analysis (area under the curve = 0.86 and 0.85, respectively). Survival time was shorter in patients with #M ≤ 200 cells/µL and LMR > 2.5. Rapidly increasing #M after treatment was related to better prognosis in patients with #M ≤ 200 cells/µL at diagnosis. Conclusions: #M at diagnosis and longitudinal changes in monocytes are related to MTB prognosis.

Child, maternal, and adult mortality in rural Ethiopia in 2019: a cross-sectional mortality survey using electronic verbal autopsies.

Background: Ethiopia, with about 10% of Africa's population, has little direct information on causes of death, particularly in rural areas where 80% of Ethiopians live. In 2019-2020, we conducted electronic verbal autopsies (e-VA) to examine causes of death and quantify cause-specific mortality rates in rural Ethiopia. Methods: We examined deaths under 70 years in the three years prior to the survey dates (November 25, 2019-February 29, 2020) among 2% of East Gojjam Zone (Amhara Region) using registered deaths and adding random sampling in this cross-sectional study. Trained surveyors interviewed relatives of the deceased with central dual-physician assignment of causes as the main outcome. We documented details on age, sex and location of death, and derived overall rural death rates using 2007 Census data and the United Nations national estimates for 2019. To these, we applied our sample-weighted causes to derive cause-specific mortality rates. We calculated death risks for the leading causes for major age groups. Findings: We studied 3516 deaths: 55% male, 97% rural, and 68% occurring at home. At ages 5 and older, injuries were notable, accounting for over a third of deaths at 5-14 years, half of the deaths at ages 15-29 years, and a quarter of deaths at ages 30-69 years. Neonatal mortality was high, mostly from prematurity/low birthweight and infections. Among children under 5 (excluding neonates), infections caused nearly two-thirds of deaths. Most maternal deaths (84%) arose from direct causes. After injuries, especially suicide, assaults, and road traffic accidents, vascular disease (15%) and cancer (13%) were the leading causes among adults at 30-69 years. HIV/AIDS and tuberculosis deaths were also important causes among adults. Interpretation: Rural Ethiopia has a high burden of avoidable mortality, particularly injury, including suicide, assaults, and road traffic accidents. Funding: International Development Research Centre, and the Canadian Institutes of Health Research.

Health in Persons Deprived of Their Liberty in South America: A Painful Reflection of Our Public Health.

Objectives: To describe sociodemographic characteristics and health-related data in persons deprived of liberty (PDL) from South America in the last five years. Methods: Documentary descriptive study. Results: There are 1.5 million PDL in Latin America and the Caribbean; the average overcrowding is 64%; 58% do not sleep in beds, 20% do not have access to clean water and 29% do not receive medical care. In Peru, during 2021, there were 87,245 PDL and 69 penal institutions. The national average overcrowding is 120%, the second-highest in South America. In South America, the prevalence of tuberculosis is 2.0% SD = 0.64 and the median of illegal substances prevalence is 34.6 (IQR = 7.5-41.4). In Peru, the prevalence of tuberculosis has decreased since 2016 (4.3%), 2018(3.5%), and 2021(2.5%). Among the health problems by country, there were more data on substance use: 8/10, and tuberculosis, 7/10 countries. Cardiovascular diseases had the least available data. Regarding COVID-19, during the first wave in Peru, 54% of the total PPL were infected, and by the end of the wave, 446 PDL and 46 members of the prison staff had died. In Colombia, between April and October 2020, there were 16,804 cases (80 in ICU) and 136 deaths. In Brazil, up to March 2021, 340 people had died, and there were over 67,000 infections. Conclusions: Overcrowding is an unresolved problem; tuberculosis and substance use are the most frequent issues. Data are limited in quality, homogeneity and availability. Greater effort is needed from health authorities to improve health management and information systematization. Source: MesH.

Spina Ventosa of the Thumb With Valgus Deformity in a Female With No Pulmonary Involvement: A First Report of Its Type in an Immunocompetent Adult From India.

Small bone involvement caused by Mycobacterium tuberculosis infection is an uncommon clinical entity. Usually, the condition is linked to the spread of bacteria from the lungs. It is rather uncommon for people without pulmonary seeding, trauma, or a history of tuberculosis to experience isolated episodes of spina ventosa. We describe a rare case of an immunocompetent Indian woman, aged 25, who complained of swelling in her left thumb. The diagnosis of primary tubercular dactylitis of the thumb was made after a thorough clinical and laboratory workup, and she received conservative treatment.

Extrapulmonary Tuberculosis Presenting As Stage V Bilateral Cervical Lymphadenitis With Cortical Cerebral Watershed Infarct Along With Maxillary and Sphenoid Sinusitis.

Extrapulmonary tuberculosis is an infrequently reported condition. However, in endemic settings, it contributes to a significant number of cases. The most common site of extrapulmonary tuberculosis is the lymph nodes. Herein, an exceedingly rare case of extrapulmonary tuberculosis presenting as bilateral cervical lymphadenitis with external cerebral watershed infarct along with sphenoid and maxillary sinusitis in an Indian male is presented. A detailed literature search revealed that a case with all these clinical conditions together has never been reported to date. A diagnostic workup supported by radiometric investigations helped in the diagnosis, and timely management was initiated.

Treatment Outcomes of Tuberculosis and Associated Factors Among Tuberculosis and Human Immunodeficiency Virus Co-infected Patients in Public Health Facilities in Jigjiga, Somali Region, Ethiopia.

BACKGROUND: Worldwide, tuberculosis (TB) is a serious public health issue, especially in low-income countries, including Ethiopia. For those who are HIV-positive, TB poses a major risk to their health. The development of chemotherapy and the effectiveness of treatment have resulted in notable increases in patient survival. The evaluation of TB treatment outcomes is an essential metric for determining the success of TB and HIV co-morbidity control strategies. PURPOSE: This study aims to identify TB treatment outcomes and associated factors among TB/HIV co-infected patients in public health facilities in Jigjiga, Somali Region, Ethiopia, in 2021. PATIENTS AND METHODS: A hospital-based cross-sectional study design was done on three facilities (Karamara, Hasan Yabare Referral Hospital, and Jigjiga Health Center) with a total of 194 study participants. Data were extracted using a checklist, entered into EpiData version 3 (The EpiData Association, Odense, Denmark), and analyzed using SPSS Statistics version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) for descriptive and inferential analysis of the study objectives. Variables in the bivariate logistic regression analysis with p-values less than 0.25 were entered into a multivariate logistic regression to identify the independent factors of TB treatment outcome. Associations were computed using an adjusted odds ratio with a 95% CI. P-values less than 0.05 were finally considered statistically significant. RESULTS: The following TB treatment outcomes were observed among all TB/HIV co-infected patients enrolled in this study: 126 (67.4%) completed treatment, three (1.8%) died, 42 (22.5%) were cured, and 16 (8.6%) were transferred out; 168 (89.8%) had a successful treatment outcome. Category of the patient (AOR = 0.194, 95% CI: 0.041, 0.923), sex of the patient (AOR = 1.490, 95% CI: 1.449, 4.951), and cotrimoxazole preventive therapy (CPT) initiation (AOR = 0.073, 95% CI: 0.021, 0.254) were found to be significant predictors for successful TB treatment outcome at a p-value less than 0.05 with a 95% CI. CONCLUSION: Overall, 89.8% of TB treatments were successful among TB/HIV co-infected patients. This study has found sex, socioeconomic status, and CPT initiation were significant factors for a successful TB treatment outcome. Based on these findings, governmental and non-governmental organizations should facilitate the implementation and enforce the availability of all TB/HIV co-infected patients.

Multidrug-Resistant Moderate Tubercular Pleural Effusion: A Rare Case Presentation.

Tuberculosis (TB) is among the most predominant infectious illnesses in developing areas around the globe. As stated by the World Health Organization (WHO), the number of instances of drug-resistant tuberculosis (DR-TB) has increased lately. This case report describes the effective diagnosis and customized treatment for primary extra-pulmonary multidrug-resistant tubercular pleural effusion, a disease which is difficult to identify due to relatively low bacterial count as well as frequently negative staining on Ziehl Neelsen (ZN) for acid-fast bacilli (AFB). The bacteria causing multidrug-resistant tuberculosis (MDR-TB) is resistant to a minimum of two drugs, isoniazid and rifampicin, the most effective TB medications. We are going to present the case of a 60-year-old male who complained of breathlessness, cough, and loss of weight for one month and chest pain and fever for 12 days. The patient's pleural fluid examination was carried out, which showed exudative fluid (according to Light's criteria) with adenosine deaminase (ADA) positive. Cartridge-based nucleic acid amplification test (CBNAAT) and line probe assays (LPAs) were carried out, which suggested mycobacterium tuberculosis (MTB) with rifampicin and isoniazid resistance. The patient was started an oral regimen with bedaquiline in accordance with WHO standards, leading to significant improvement. This case reveals that to promptly diagnose and treat DR-TB, pleural effusions, and pleural biopsies need to be exposed early to investigations such as Xpert (MTB)/resistance to rifampicin assay, culturing, and genotype drug sensitivity testing (DST).

Survival Rate and Predictors of Mortality Among TB-HIV Co-Infected Patients During Tuberculosis Treatment at Public Health Facilities in Bahir Dar City, Northwest Ethiopia.

Background: Tuberculosis and human immunodeficiency virus co-infection pose a major public health concern, particularly in developing countries. The survival and predictors of mortality were not sufficiently studied among TB-HIV co-infected patients in Ethiopia. Objective: This study aimed to investigate the survival rate and predictors of mortality among TB-HIV co-infected patients during TB treatment at public health facilities in Bahir Dar, Northwest Ethiopia. Methods: A retrospective follow-up study was conducted among 401 TB-HIV co-infected patients who were treated for tuberculosis between July 2018 and June 2022 at public health facilities in Bahir Dar city, Ethiopia. Data were collected using a structured checklist from patient charts. Data entry and analysis were done using EpiData 3.1 and Stata version 15, respectively. A Cox proportional Hazard regression model was used to identify predictors of mortality. Predictors with P < 0.05 in the multivariable regression were considered statistically significant. Results: Among the 401 TB-HIV co-infected patients, 59 (14.7%) died during the follow-up period. Predictors like lower BMI (AHR = 3.00, 95% CI = 1.44, 6.28), extrapulmonary TB infection (AHR = 3.30, 95% CI = 1.50, 7.29), presence of opportunistic infection (AHR = 5.07, 95% CI = 2.55, 10.08), functional status (bedridden: AHR = 4.49, 95% CI = 1.63, 12.33), and adherence to TB treatment (fair = AHR = 2.74, 95% CI = 1.41, 7.20, and poor = AHR = 3.75, 95% CI = 1.52, 9.23) were associated with mortality. Conclusion: Mortality among TB and HIV coinfected people was high at public health facilities in Bahir Dar city. This result suggested that in order to increase patient survival, it would be necessary to enhance nutritional status, increase adherence to TB treatment, and prevent opportunistic infections.

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial.

BACKGROUND: Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. METHODS: This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. FINDINGS: Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2-11] vs 4% [1-13], p=0·62; respiratory 7% [1-19] vs 4% [1-9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5-17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [-1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported-a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. INTERPRETATION: This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

Dual-centre evaluation of the FluoroType MTBDR version 2 assay for detection of Mycobacterium tuberculosis complex and resistance-conferring mutations in pulmonary and extrapulmonary samples from Denmark, Germany and Sierra Leone.

OBJECTIVE: We evaluated the ability of FluoroType MTBDR version 2 (FTv2; Hain Lifescience), a second-step real-time PCR assay, to simultaneously detect Mycobacterium tuberculosis complex (MTBC) DNA and mutations conferring resistance to rifampicin (RIF) and isoniazid (INH), in pulmonary and extrapulmonary samples from patients and compared them with corresponding cultures. METHODS: FTv2 MTBC was evaluated on 1815 and 432 samples from Denmark (DK) and Germany (DE). RIF and INH resistance mutations were assessed in the German samples and 110 samples from Sierra Leone and subsequently compared to phenotypic antimicrobial susceptibility testing and a composite reference DNA (CRD) based on the GenoType MTBDR line-probe assay and Sanger sequencing or whole genome sequencing. RESULTS: Of the 584 [557 smear-negative] Danish and 277 [85 smear-negative] German sputum samples, 42 [16] and 246 [54] were culture positive, and 44 [18] and 222 [35] were FTv2 positive, providing an FTv2 sensitivity and specificity of 0.86 [0.63] and 0.98 (DK), 0.90 [0.65] and 1.00 (DE), respectively. The count, sensitivities, and specificities for all pulmonary samples were 1434, 0.79, and 0.99 (DK) and 347, 0.86, and 1.00 (DE), respectively; for extrapulmonary samples, 381, 0.33, 0.99 (DK) and 83, 0.50, and 1.00 (DE). The valid count, sensitivity, and specificity compared with CRD for detecting resistance mutations were RIF 355, 0.99, 0.96, and INH 340, 1.00, and 0.98, respectively. CONCLUSION: FTv2 reliably detects MTBC DNA in pulmonary and extrapulmonary samples and detects resistance mutations for INH and RIF resistance in inhA promoter, katG, and rpoB genes.