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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124943, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39146629

RESUMO

The use of a conjugate N-containing ligand resulted in the decreasing of structural dimensions from 2D network of [Tb(2-pyia)(Ac)(H2O)] (CP1) to 1D chain [Tb(2-pyia)(Ac)(IDP)] (CP2) (2-H2pyia = 5-(pyridin-2-ylmethoxy) isophthalic acid and IDP=imidazo[4,5-f]-[1,10] phenanthroline). Both of them exhibit the characteristic luminescence of Tb ions and could have high fluorescence sensing properties for cefixime and fluridine. The different sensing properties for nitro explosives are manifested as CP1 for nitrobenzene and CP2 for 4-nitrophenol due to the difference in structure. Furthermore, CP2 exhibits the ratiometric fluorescence sensing for Fe3+ ion with a low detection limit of 0.405 µM. The fluorescence sensing mechanism of the two Tb complexes for different analytes was investigated using experimental methods and theoretical calculations. CP1 was used for the detection of Flu residues in the actual system and better results were obtained. The work shows the introduction of the chelated ligand might affect the structural and sensing performance changes of coordination polymers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39391117

RESUMO

Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy is a relatively new and poorly recognized autoimmune cause of meningoencephalomyelitis. Our case highlights the challenging nature of diagnosing this rare condition as its broad constellation of radiographic findings and spectrum of presentation may mimic many other etiologies of encephalopathy, particularly infectious causes such as Tuberculosis (TB) meningitis.

3.
Cureus ; 16(8): e68309, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39350855

RESUMO

Although rare, musculoskeletal involvement of tuberculosis (TB) sustains this disease as a global health problem. Hip TB presents some unique challenges to its diagnosis and cure because of its specific anatomical and biomechanical properties. Herein, we would like to highlight an integrated approach in the surgical intervention and rehabilitation towards the management of an advanced symptom-bearing 25-year-old female hip TB patient. She had taken treatment for tuberculosis, but even then, her right hip was painful, and movements were severely restricted. Imaging revealed severe destruction of the hip joint; a bone biopsy confirmed tuberculous osteomyelitis of the hip joint. Total hip replacement (THR) revealed the severe destruction of the hip joint by imaging and was found positive by bone biopsy for tuberculous osteomyelitis. The rehabilitation after the surgery consisted of measures for pain control, mobility training exercises, muscle strengthening, and balance training exercises. After six weeks of THR, the patient showed considerable improvement in pain level, flexibility, muscle strength, and functional status during assessments. What is highlighted is the complexity that lies in the management of TB of the hip, which requires the multidisciplinary approach that the case above calls for. In the future, more sophisticated diagnostics and newer therapies should be patient-reported and outcome-oriented. Larger multicenter studies directed to the various populations would be beneficial in this direction. The small size of the study, its single-center dimension, and the short follow-up limited broader applicability and long-term insights.

4.
BMC Infect Dis ; 24(1): 1110, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375585

RESUMO

BACKGROUND: The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored. METHODS: Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant. RESULTS: Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01-1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study. CONCLUSIONS: In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.


Assuntos
Testes de Liberação de Interferon-gama , Transplante de Rim , Tuberculose Latente , Transplantados , Humanos , Tuberculose Latente/diagnóstico , Feminino , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Testes de Liberação de Interferon-gama/métodos , Estudos Prospectivos , Adulto , Isoniazida/uso terapêutico , Antituberculosos/uso terapêutico , Programas de Rastreamento/métodos
5.
Clin Infect Dis ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39378332

RESUMO

BACKGROUND: In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. METHODS: In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). RESULTS: Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). CONCLUSIONS: The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

6.
Cureus ; 16(9): e68784, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39371702

RESUMO

Human immunodeficiency virus (HIV) and tuberculosis (TB) are two of the most pressing global health issues, each contributing significantly to morbidity and mortality worldwide. This review provides a comprehensive analysis of HIV-associated TB (HIV-TB), focusing on the clinical challenges and advancements in its management. HIV-positive individuals are at a heightened risk of developing active TB due to the immunosuppressive effects of the virus, which complicates both diagnosis and treatment. The interplay between these two diseases exacerbates health outcomes, presenting unique challenges related to drug interactions, adherence to treatment regimens, and management of adverse effects. This review explores the current diagnostic approaches, including advances in testing technologies and screening strategies, and examines treatment protocols, highlighting the integration of antiretroviral therapy with TB treatment. Special considerations for managing HIV-TB in various populations, such as children, pregnant women, and the elderly, are discussed. Additionally, the review addresses public health strategies for prevention and the impact of socio-economic and healthcare system factors on disease management. Finally, it highlights recent research innovations and future directions aimed at improving outcomes for individuals with HIV-TB. By synthesizing the latest evidence and clinical practices, this review aims to enhance understanding and guide effective management of this critical co-infection, ultimately contributing to reduced global burden and improved patient care.

7.
Cureus ; 16(9): e68733, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39371708

RESUMO

Tuberculosis involving the thyroid gland is an exceptionally rare condition with varied clinical presentations, often leading to diagnostic challenges. We report two cases: a 9-year-old male with necrotic tuberculous cervical lymphadenopathy secondarily involving the thyroid gland, and a 40-year-old male with disseminated tuberculosis affecting multiple organ systems, including the thyroid gland. Both cases presented with swelling over the neck region and were evaluated using ultrasonography and contrast-enhanced computed tomography (CECT), which revealed characteristic imaging findings of thyroid involvement. Fine-needle aspiration cytology (FNAC) and TB-PCR (polymerase chain reaction for Mycobacterium tuberculosis) of the aspirate confirmed the diagnosis of tuberculosis. Early identification and medical management with anti-tubercular therapy led to successful treatment, thereby avoiding unnecessary surgical interventions. These cases signify the importance of considering thyroid tuberculosis in the differential diagnosis of thyroid lesions, especially in endemic regions, and highlight the role of imaging and FNAC in establishing a prompt diagnosis.

8.
Cureus ; 16(9): e68665, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39371792

RESUMO

Tuberculosis (TB) peritonitis resulting in a small bowel obstruction is uncommon and can be a challenging infectious disease to diagnose. It often has an insidious onset with non-specific symptoms. Today we report a rare case of a 30-year-old woman who recently traveled to Vietnam and presented with worsening upper and lower gastrointestinal symptoms. CT scan revealed an ill-defined mass in the terminal ileum with prominent mucosal enhancement and wall thickening, which ultimately led to subsequent colonoscopy and Quantiferon Gold testing, revealing a positive result. Biopsy of the mass demonstrated noncaseating granulomatous colitis with rare acid-fast positive bacillus consistent with mycobacterial infection. As a result, the patient was ultimately initiated on antituberculosis therapy. Shortly thereafter, she was readmitted with clinical features suggestive of a bowel obstruction. The patient was managed with supportive care and did not require surgical intervention. However, approximately two months following the readmission, she presented to the emergency department once again with a mechanical bowel obstruction that ultimately required surgery. This case underscores the importance of TB testing in patients with insidious, worsening gastrointestinal symptoms and highlights the potential complications of TB peritonitis, even in those undergoing antituberculosis treatment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39374650

RESUMO

OBJECTIVES: In high TB burden countries like Bangladesh, research and policies tend to focus on rifampicin (RIF)-resistant TB patients, leaving RIF sensitive but isoniazid (INH) resistant (Hr-TB) patients undiagnosed. Our study aims to determine the prevalence of INH resistance among pulmonary TB (PTB) patients in selected healthcare facilities in Bangladesh. METHODS: This study was conducted across nine TB Screening and Treatment Centers situated in Bangladesh. Sputum samples from 1084 Xpert-positive PTB patients were collected between April 2021 and December 2022, and cultured for drug susceptibility testing (DST). Demographic and clinical characteristics of Hr-TB and drug-susceptible TB patients were compared. RESULTS: Among available DST results of 998 culture positive isolates, resistance rate of any INH regardless of RIF susceptibility was 6.4% (64/998, 95% CI, 4.9-8.2). The rate was significantly higher in previously treated (21.1%, 16/76, 95% CI, 12.0-34.2) compared to newly diagnosed TB patients (5.2%, 48/922, 95% CI, 3.8-6.9) (p <0.001). The rate of Hr-TB was 4.5% (45/998, 95% CI, 3.3-6.0), which was also higher among previously treated (6.6%, 5/76, 95% CI, 1.4-13.5) compared to newly diagnosed TB patients (4.3%; 40/922, 95% CI, 3.1-5.9) (p=0.350). Most importantly, the rate of Hr-TB was more than double compared to MDR-TB (4.5%, 45/998, vs 1.9%, 19/998) found in the current study. CONCLUSIONS: This study reveals a high prevalence of Hr-TB, surpassing even that of the MDR-TB in Bangladesh. This emphasizes the urgent need to adopt WHO-recommended molecular tools at the national level for rapid detection of INH resistance so that patients receive timely and appropriate treatment.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39377922

RESUMO

Drug-resistant tuberculosis (DR-TB) represents a pressing global health issue, leading to heightened morbidity and mortality. Despite extensive research efforts, the escalation of DR-TB cases underscores the urgent need for enhanced prevention, diagnosis, and treatment strategies. This review delves deep into the molecular and genetic origins of different types of DR-TB, highlighting recent breakthroughs in detection and diagnosis, including Rapid Diagnostic Tests like Xpert Ultra, Whole Genome Sequencing, and AI-based tools along with latest viewpoints on diagnosis and treatment of DR-TB utilizing newer and repurposed drug molecules. Special emphasis is given to the pivotal role of novel drugs and discusses updated treatment regimens endorsed by governing bodies, alongside innovative personalized drug-delivery systems such as nano-carriers, along with an analysis of relevant patents in this area. All the compiled information highlights the inherent challenges of current DR-TB treatments, discussing their complexity, potential side effects, and the socioeconomic strain they impose, particularly in under-resourced regions, emphasizing the cost-effective and accessible solutions. By offering insights, this review aims to serve as a compass for researchers, healthcare practitioners, and policymakers, emphasizing the critical need for ongoing R&D to improve treatments and broaden access to crucial TB interventions.

11.
Indian J Tuberc ; 71 Suppl 2: S203-S207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39370184

RESUMO

BACKGROUND: TB stigma represents a growing threat to TB care. Understanding TB stigma distribution and associating factors is crucial for effective TB control in Afghanistan. OBJECTIVES: To profile the prevalence of TB-related stigma and its associating factors among TB patients in Southern Afghanistan. METHODS: In this multi-center cross-sectional study, we randomly recruited 603 adult TB patients from 2 major TB treatment sites in Southern Afghanistan. A score of >8 on the Stigma Scale for Chronic Illness-8 items (SSCI-8 items) was considered as positive for TB-related stigma. We fitted a binary logistic regression model. RESULTS: Out of the 603 TB patients included in this study, 88.3% (95%CI: 85.8-90.9%) had TB-related stigma using the SSCI-8 cutoff (>8). Being in the age group 18-40 years, rural residence, no formal education, severe perception of illness, lack of TB knowledge, and symptoms of depression had positive associations with TB stigma. CONCLUSION: A considerable percentage (88.3%) of patients had TB stigma. We identified potential risk factors that could serve as a benchmark for guiding policy efforts and interventions that aim to reduce stigma among TB patients in Afghanistan.


Assuntos
Estigma Social , Humanos , Afeganistão/epidemiologia , Estudos Transversais , Adulto , Masculino , Feminino , Prevalência , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Fatores de Risco , Tuberculose/epidemiologia , Tuberculose/psicologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/psicologia , Depressão/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde
12.
Indian J Tuberc ; 71 Suppl 2: S245-S249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39370191

RESUMO

BACKGROUND: Tuberculosis (TB) is a pressing public health issue in many developing countries, with India having the highest number of cases. Lack of awareness and stigmatization of TB remains a significant barrier to addressing this challenge. This paper examines the perceived causes and stigma associated with TB among Apatani tribe of Arunachal Pradesh. METHODS: The study employed a mixed research approach, involving 106 TB patients (both pulmonary and extrapulmonary), both current and retrospective cases, from the Apatani tribe in Ziro valley, Arunachal Pradesh. Participants were selected from all the seven traditionally divided villages using purposive sampling. Semi-structured pre-tested schedules were used to conduct interviews with the patients. RESULTS: Among participants, 29.24% attributed TB to transmission, 34.91% had alternative explanations, and 35.85% remained uncertain about the causes. Notably, more Pulmonary TB patients reported transmission as the cause. A 10.75% higher likelihood of having misconceptions was observed among males. Literate individuals had 13.27% greater chance of being aware, although, higher education levels did not consistently follow this trend. Perceived stigmatization was evident mainly due to the contagious nature of the disease. CONCLUSION: A significant knowledge gap was evident among TB patients, with very few having a clear understanding of the causes of this disease. Gender differences in this regard were minimal. Literate individuals were more likely to understand the causes. Additionally, perceived stigmatization was a notable concern in the study.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Estigma Social , Tuberculose Pulmonar , Humanos , Índia , Masculino , Feminino , Adulto , Tuberculose Pulmonar/psicologia , Pessoa de Meia-Idade , Tuberculose/psicologia , Adulto Jovem , Estudos Retrospectivos , Adolescente , Estereotipagem
13.
Indian J Tuberc ; 71 Suppl 2: S258-S263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39370193

RESUMO

BACKGROUND: This study aimed to determine the prevalence of TB among patients living with HIV in Patna district, India. It also assessed the factors contributing to co-infection and evaluated patients' quality of life. METHODS: This cross-sectional study was conducted at the Antiretroviral Therapy (ART) Centre in Patna, India, for a period of eight months. The socio-demographic information was collected through a pre-defined semi-structured questionnaire administered by the interviewer during face-to-face interviews at the time of enrolment. Clinical details were obtained from the hospital records. The statistical analysis was performed using SPSS software. RESULTS: The study showed that out of 289 people living with HIV, 31% had TB as a co-infection. Male patients had a higher probability of contracting HIV-TB co-infection compared to female patients. The study indicated that advanced WHO staging, male gender, past history of TB, and opportunistic infections were strong predictors. Conversely, the odds of HIV-TB co-infection reduced with a CD4 count of over 300 cells/mm3. However, an increase in age, lower socio-economic status, BMI below the normal range, and presence of comorbidities might increase the odds of HIV-TB co-infection but were not statistically significant. The QoL of HIV-TB patients was significantly lower than that of HIV-only patients. CONCLUSIONS: People with low CD4+ T cell count are at a higher risk of developing TB due to HIV/TB co-infection. The baseline clinical staging of HIV is significantly correlated with TB co-infection. Those in WHO Clinical Stage III and IV have a four times higher risk of developing TB.


Assuntos
Coinfecção , Infecções por HIV , Qualidade de Vida , Humanos , Masculino , Índia/epidemiologia , Feminino , Adulto , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Estudos Transversais , Coinfecção/epidemiologia , Pessoa de Meia-Idade , Prevalência , Tuberculose/epidemiologia , Contagem de Linfócito CD4 , Tuberculose Pulmonar/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fatores Sexuais , Adulto Jovem , Fatores de Risco
14.
BMC Infect Dis ; 24(1): 1087, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354416

RESUMO

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens. METHODS: We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050). RESULT: We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care. CONCLUSION: Treatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens.


Assuntos
Antituberculosos , Metanálise em Rede , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Rifampina/uso terapêutico , Antituberculosos/uso terapêutico , Antituberculosos/efeitos adversos , Resultado do Tratamento , Mycobacterium tuberculosis/efeitos dos fármacos
15.
Cureus ; 16(9): e68421, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39360094

RESUMO

India has a high burden of drug-resistant tuberculosis (DR-TB) cases. The management of this severe form of TB is associated with a number of issues like long treatment durations, high pill burden, and multiple adverse drug reactions. Efforts are on through various research studies and trials for finding solutions to the issues linked to the current drug regimens against drug-resistant tuberculosis. One such remarkable development is the introduction of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM)-based regimens to fight against two of the most severe forms of tuberculosis, i.e., multidrug- and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB). This editorial throws light on this newer regimen and discusses the same in the Indian context.

16.
Microbiol Spectr ; : e0124624, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361873

RESUMO

Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains. Herein, we design and synthesize 35 novel benzo[c]phenanthridine derivatives (BPDs). The two most potent compounds, BPD-6 and BPD-9, accumulated within the bacterial cell and exhibited strong inhibitory activity (MIC90 ~2 to 10 µM) against multiple Mycobacterium strains while remaining inactive against a range of other Gram-negative and Gram-positive bacteria. BPD-6 and BPD-9 were also effective in reducing Mtb survival within infected macrophages, and BPD-9 reduced the burden of Mycobacterium bovis BCG in the lungs of infected mice. The two BPD compounds displayed comparable efficacy to rifampicin (RIF) against non-replicating Mtb (NR-Mtb). Importantly, BPD-6 and BPD-9 inhibited the growth of multiple MDR Mtb clinical isolates. Generation of BPD-9-resistant mutants identified the involvement of the Mmr efflux pump as an indirect resistance mechanism. The unique specificity of BPDs to Mycobacterium spp. and their efficacy against MDR Mtb isolates suggest a potential novel mechanism of action. The discovery of BPDs provides novel chemical scaffolds for anti-TB drug discovery.IMPORTANCEThe emergence of drug-resistant tuberculosis (TB) is a serious global health threat. There remains an urgent need to discover new antibiotics with unique mechanisms of action that are effective against drug-resistant Mycobacterium tuberculosis (Mtb). This study shows that novel semi-synthetic compounds can be derived from natural compounds to produce potent activity against Mtb. Importantly, the identified compounds have narrow spectrum activity against Mycobacterium species, including clinical multidrug-resistant (MDR) strains, are effective in infected macrophages and against non-replicating Mtb (NR-Mtb), and show anti-mycobacterial activity in mice. These new compounds provide promising chemical scaffolds to develop potent anti-Mtb drugs of the future.

17.
Radiol Case Rep ; 19(12): 6609-6613, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39380834

RESUMO

Tuberculosis (TB) of the musculoskeletal system is an uncommon manifestation, accounting for only 1-3% of all TB cases and typically affects the spine and large joints. Isolated TB of the foot is even rarer, comprising less than 10% of osteoarticular TB. Tuberculous osteomyelitis, where the infection is limited to the bone without joint involvement, is an even more uncommon presentation. A 55-year-old male with a history of fall presented with chronic left foot pain and swelling. Initial workup led to a misdiagnosis of Charcot foot. Despite treatment with analgesics and intra-articular platelet-rich plasma injections, symptoms still persisted for several months. MRI revealed inflammation in multiple joints with bone damage (erosions & edema) along with reduced joint space in talonavicular joint and Mycobacterium tuberculosis was identified on interferon gamma release assay. The patient was ultimately diagnosed with diffuse osteoarticular tuberculosis and tuberculous osteomyelitis of the left foot and commenced on anti-tubercular therapy. After few months symptoms were resolved and patient was tested negative for TB. Our case highlights the importance of maintaining a high index of suspicion for osteoarticular tuberculosis, even in the absence of pulmonary involvement, especially in immunocompromised patients like diabetics. This case emphasizes the importance of a multidisciplinary approach for accurate diagnosis and effective management of such challenging presentation.

18.
Cureus ; 16(8): e67716, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39318901

RESUMO

BACKGROUND: Tuberculosis (TB) continues to pose a significant public health challenge globally. Despite efforts to meet targets set by the End-TB Strategy, progress has been slow. Health-seeking practices that decide approaches to various sectors of healthcare providers result in inappropriate diagnosis and lack of awareness regarding available standard treatment, indicating inaccuracy in estimated incidences and underreporting. OBJECTIVE: This study was designed to map the patient pathways for Persons with Tuberculosis (PwTB) from their initial point of contact through to diagnosis and treatment. It aimed to identify the socio-demographic characteristics and profiles of PwTB, as well as their choice of healthcare facilities, that influenced care-seeking behavior throughout the TB care cascade. METHODS: A cross-sectional study was conducted from January to July 2022 in Jharkhand and Gujarat, India. Data were collected from 997 PwTB using a pre-designed structured questionnaire, covering socio-demographic profiles, TB profile of PwTB, and care-seeking behavior. The study analyzed the number and types of facilities visited, categorized the data, and used chi-square and binary logistic regression tests to identify significant associations. RESULTS: In a study of 965 TB patients, 58.8% were male, and 61.3% were aged 18-40. Patients visited an average of two healthcare facilities, with significant associations found between age, occupation, comorbidity status, and facility switching (p < 0.005). Public health facilities were the primary point of care, with 91.4% using them for first consultations and 80.6% for treatment. Regression analysis highlighted significant predictors of care-seeking behavior, underscoring the need to enhance public healthcare infrastructure. CONCLUSION: Understanding patient pathways and the factors influencing care-seeking behavior is crucial for improving TB management. Strengthening public healthcare infrastructure and enhancing coordination between public and private sectors can reduce transitions and ensure timely and appropriate care.

19.
Radiol Case Rep ; 19(12): 5908-5915, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39319173

RESUMO

Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis, an infectious disease endemic in developing countries. Indonesia is ranked second only to India in terms of TB incidence in the world. TB generally manifests in the respiratory system, which can then spread hematogeneously or lymphogeneously to extrapulmonary organs. Intracranial tuberculoma is a rare manifestation of TB when compared to the overall TB presentation. Central nervous system involvement ranges from 2-5% and increases to 15% in cases of AIDS-related TB, with the percentage of tuberculoma findings around 1% in other intracranial TB cases. The most common manifestation is tuberculous meningitis. Central nervous system (CNS) involvement is a severe manifestation of TB, with high mortality and neurological morbidity. In this case report, the author presented a 6-year-old girl with giant cerebral tuberculoma, which, at the time of surgery, resembled a neoplasm with a nonspecific history of TB. MRI can visualize abnormalities with specific characteristics; Clinically and radiologically, CNS TB can mimic other infections or noninfectious conditions such as neoplasms. Therefore, clinicians can take appropriate management actions in order to prevent mortality and disability due to sequelae in CNS TB cases.

20.
Heliyon ; 10(18): e37583, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309911

RESUMO

Understanding how the bacteriomes in tuberculous lesions can be influenced by the susceptibility of Mycobacterium tuberculosis (MTB) can provide valuable information for preventing and treating drug resistant tuberculosis (DR-TB). High-throughput 16S rRNA sequencing was employed to analyze the bacteriome in pulmonary TB lesions from 14 patients with DR-TB and 47 patients with drug sensitive tuberculosis (DS-TB), along with 18 normal lung tissues (NT) from 18 lung cancer patients serving as the bacterial baseline. The phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) algorithm was utilized to predict bacterial metabolic functions. The major phyla of pulmonary bacteriomes included Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Fusobacteria. Alpha diversity indices, including ACE, Chao1, Shannon and OTU observed, all demonstrated different bacterial communities of DS-TB samples from that of NT samples; while only Shannon indicated difference between DR-TB and NT samples. The analysis of similarity (ANOSIM) showed significantly different bacterial communities within TB lesions compared to NT samples (R = 0.418, p = 0.001). However, difference was not observed between DR-TB and DS-TB samples (ANOSIM, R = 0.069, p = 0.173). The bacterial profiles within each DR-TB individual appeared unique, with no obvious clusters corresponding to drug-resistant phenotypes. Nevertheless, indicator genera identified in DR-TB and DS-TB lesions demonstrated distinctive micro-ecological environments. Most COG functions were enriched in TB lesions, and the most significant one was [J] translation, ribosomal structure and biogenesis. The distinct enrichment patterns of bacterial enzymes in DR-TB and DS-TB lesions suggest that pulmonary bacterial activities can be modulated by the susceptibility of MTB bacilli. This study provides fresh perspectives and strategies for the precise diagnosis and assessment of drug resistance tuberculosis.

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