Challenge Of Tuberculosis Research Articles

Deciphering the diagnostic challenges of female genital tuberculosis: Insights from women pursuing conception at a tertiary care centre in northern India.

Female genital tuberculosis (FGTB) is asymptomatic or may present with a few symptoms among which infertility is the most common. The diagnosis of FGTB is challenging, as there is no single diagnostic test available.We researched 50 infertile patients by various special investigations and found 50% had tuberculosis, by various means. Endometrial biopsy and Hystero-laparoscopy are complementary procedures, and Cartridge Based Nucleic Acid Amplification Test is a useful new addition to the diagnostic armamentarium for endometrial and peritoneal samples.

Synthesis and InhA Inhibition of Imidazo[1,2-a]pyridine Derivatives as Anti-Tuberculosis Agents

Abstract: Imidazopyridine holds significance as a crucial fused bicyclic heterocycle within the realm of medicinal chemistry, being acknowledged as a "privileged scaffold" owing to its extensive utility. Numerous methodologies for the synthesis of imidazo[1,2-a]pyridines have been documented, with a considerable focus on strategies aimed at functionalizing these compounds. This study aimed to explore the potential of novel imidazo[1,2- a] pyridine derivatives as agents against drug-resistant Mycobacterium tuberculosis, which poses significant challenges in tuberculosis (TB) treatment. The research involved the synthesis of substituted imidazo[1,2- a]pyridine derivatives using site identification and molecular docking techniques. Characterization of the synthesized compounds was carried out using FT-IR, LC-MS, 1H NMR, and 13C NMR analysis. Compounds 6a and 6k showed good anti-TB activity against the H37Rv strain of Mycobacterium tuberculosis, with MIC values of 0.6 μM and 0.9 μM, respectively, which were comparable with the standard drug isoniazid. These findings suggest that imidazo[1,2-a]pyridine derivatives, especially compounds 6a and 6k, have potential as agents against drug-resistant TB, providing valuable insights for ongoing efforts in developing effective TB treatments.

Emergence of antibiotic-specific Mycobacterium tuberculosis phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiologic state of M. tuberculosis (Mtb) which may enable the pathogen to withstand treatment. While antibiotic-treated Mtb have been evaluated in short-term in vitro experiments, it is unclear if and how long-term in vivo treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affect Mtb physiologic states differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the Mtb transcriptome in the BALB/c high-dose aerosol infection mouse model following 4-week treatment with three sterilizing and three non-sterilizing antibiotics. Certain transcriptional changes were concordant among most antibiotics, including decreased expression of genes associated with protein synthesis and metabolism, and the induction of certain genes associated with stress responses. However, the magnitude of this concordant response differed between antibiotics. Sterilizing antibiotics rifampin, pyrazinamide, and bedaquiline generated a more quiescent Mtb state than did non-sterilizing antibiotics isoniazid, ethambutol, and streptomycin, as indicated by decreased expression of genes associated with translation, transcription, secretion of immunogenic proteins, metabolism, and cell wall synthesis. Additionally, we identified distinguishing transcriptional effects specific to each antibiotic, indicating that different mechanisms of action induce distinct patterns of cellular injury. In addition to elucidating Mtb physiologic changes associated with antibiotic stress, this study demonstrates the value of SEARCH-TB as a highly granular pharmacodynamic assay that reveals antibiotic effects that are not apparent based on culture alone.

Farmer‐led badger vaccination in Cornwall: Epidemiological patterns and social perspectives

Abstract In the United Kingdom, the management of bovine tuberculosis (bTB) challenges the coexistence of people and wildlife. Control of this cattle disease is hindered by transmission of its causative agent, Mycobacterium bovis, between cattle and badgers Meles meles. Badger culling has formed an element of bTB control policy for decades, but current government policy envisions expanding badger vaccination. Farming leaders are sceptical, citing concerns that badger vaccination would be impractical and potentially ineffective. We report on a 4‐year badger vaccination initiative in an 11 km2 area which, atypically, was initiated by local farmers, delivered by scientists and conservationists, and co‐funded by all three. Participating landholders cited controversies around culling and a desire to support neighbours as their primary reasons for adopting vaccination. The number of badgers vaccinated per km2 (5.6 km−2 in 2019) exceeded the number culled on nearby land (2.9 km−2 in 2019), and the estimated proportion vaccinated (74%, 95% confidence interval [CI] 40%–137%) exceeded the 30% threshold predicted by models to be necessary to control M. bovis. Farmers were content with how vaccination was delivered, and felt that it built trust with wildlife professionals. The percentage of badgers testing positive for M. bovis declined from 16.0% (95% CI 4.5%–36.1%) at the start of vaccination to 0% (95% CI 0%–9.7%) in the final year. With neither replication nor unvaccinated controls, this small‐scale case study does not demonstrate a causal link between badger vaccination and bTB epidemiology, but it does suggest that larger‐scale evaluation of badger vaccination would be warranted. Farmers reported that their enthusiasm for badger vaccination had increased after participating for 4 years. They considered vaccination to have been effective, and good value for money, and wished to continue with it. Synthesis and applications: Although small‐scale, this case study suggests that badger vaccination can be a technically effective and socially acceptable component of bTB control. A wider rollout of badger vaccination is more likely if it is led by the farming community, rather than by conservationists or government, and is combined with scientific monitoring. Read the free Plain Language Summary for this article on the Journal blog.

Diagnostic and therapeutic challenges of tuberculosis in kidney transplant recipients; a case series study

Diagnostic and therapeutic challenges of tuberculosis in kidney transplant recipients; a case series study

Regulatory role of Mycobacterium tuberculosis MtrA on dormancy/resuscitation revealed by a novel target gene-mining strategy.

The unique dormancy of Mycobacterium tuberculosis plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate. To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites. The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.7% of the binding sites were located inside the target genes. The functions of 288 potential MtrA target genes predicted according to 294 confirmed binding sites were highly diverse, and DNA replication and damage repair, lipid metabolism, cell wall component biosynthesis, cell wall assembly, and cell division were the predominant pathways. Among the 53 pathways shared between dormancy/resuscitation and persistence, which accounted for 81.5% and 93.0% of the total number of pathways, respectively, MtrA regulatory genes were identified not only in 73.6% of their mutual pathways, but also in 75.4% of the pathways related to dormancy/resuscitation and persistence respectively. These results suggested the pivotal roles of MtrA in regulating dormancy/resuscitation and the apparent relationship between dormancy/resuscitation and persistence. Furthermore, the finding that 32.6% of the MtrA regulons were essential in vivo and/or in vitro for M. tuberculosis provided new insight into its indispensability. The findings mentioned above indicated that MtrA is a novel promising therapeutic target for tuberculosis treatment since the crucial function of MtrA may be a point of weakness for M. tuberculosis.

Genetic analysis of pyrazinamide resistance: mutations in the pncA gene among clinical isolates of multi-drug resistant Mycobacterium Tuberculosis

Pyrazinamide (PZA) resistance presents a significant challenge in tuberculosis (TB) management, particularly in multi-drug resistant (MDR) cases. Understanding the genetic basis of PZA resistance is crucial for effective treatment strategies. This review provides a comprehensive overview of recent advancements in molecular characterization of PZA resistance, focusing on mutations in the pncA, rpsA, and panD genes. We discuss the prevalence of PZA resistance, mechanisms of resistance, and the utility of genetic analysis in early diagnosis. Key findings from studies investigating PZA resistance in clinical isolates are summarized, highlighting the predominant role of pncA mutations. Additionally, we explore the significance of mutations in rpsA and panD genes, elucidating alternative pathways to PZA resistance. Insights from genetic analysis have implications for personalized treatment approaches and TB control programs. Future directions in research and the potential of molecular methods in enhancing PZA susceptibility testing are also discussed.

In vitro evaluation of the binding activity of novel mouse IgG1 opsonic monoclonal antibodies to Mycobacterium tuberculosis and other selected mycobacterial species

Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of Mycobacterium tuberculosis, M. avium, M. bovis, M. fortuitum, M. intracellulare, and M. smegmatis American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant M. tuberculosis strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the M. tuberculosis resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 µg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.

Biosecurity Challenges: How Defense Strategies Against Tuberculosis In Asean Countries

This comprehensive research provides a thorough analysis of tuberculosis (TB) incidence trends and sanitation challenges within the ASEAN region spanning from 2005 to 2021. It underscores the critical need for robust defense strategies against TB, particularly in light of setbacks exacerbated by the COVID-19 pandemic. The research, conducted in Jakarta, Indonesia, from June to July 2023, delved into biosecurity challenges of tuberculosis in ASEAN countries, using a quantitative approach and cross-sectional design. Data from 2005 to 2021, sourced from the ASEAN database, underwent descriptive statistics and trend analysis to explore TB incidence rates, ensuring a comprehensive investigation scope. The study places emphasis on the imperative of implementing comprehensive measures encompassing prevention, screening, swift diagnosis, utilization of advanced treatment regimens, and ensuring robust patient support systems. Moreover, it highlights the pivotal role of addressing sanitation challenges, as substandard conditions significantly heighten the risks of TB transmission. The study's scope encompasses an array of critical subjects, with a central focus on TB incidence rates, as well as the crucial aspects of access to improved sanitation facilities and sanitation services. The conclusion is the ASEAN region, especially the Philippines, faces a notable tuberculosis burden, coupled with uneven access to sanitation. Effective interventions and collaboration are vital for improving public health and sanitation standards in ASEAN countries.

Multi-Drug Resistance Tuberculosis (MDR-TB) Challenges in India: A Review.

Tuberculosis (TB) is an increasing public health concern in India. The development of resistance to two of the most effective medications, rifampicin, and isoniazid, is the largest worldwide challenge in the management of TB. An epidemiological indicator used to evaluate the effectiveness of the TB management program is the initial medication resistance level. Our search for published papers in English using Medical Subject Heading phrases was conducted through PubMed, Google Scholar, and Scopus. We also looked through several official sources to learn the most recent information on multi-drug resistance in India. Multi-drug resistance tuberculosis is a significant risk to human health globally. Stigmatization or discrimination of those who have TB or who are impacted by it can make the disease more difficult to manage medically and socially, and it is ultimately responsible for missed opportunities for diagnosis and treatment, interruptions of care, and unsuccessful outcomes. Eliminating TB is complicated by stigma.

The diagnostic challenge of gastrointestinal tuberculosis mimicking colon cancer: A case report

Gastrointestinal tuberculosis (TB) accounts for 3.5% of extrapulmonary TB cases and is associated with active or inactive pulmonary TB in 76% of cases. A 53-year-old lady with no prior history of morbidity visited our hospital's department with weakness, an inability to eat, a 39°C fever, no chills, and night sweats that had been present for about six months. Additionally, a colonoscopy revealed a mamelonated mass of a stenotic character in the ascending colon, along with minor mesenteric adenitis, on computed tomography scans of the abdomen and pelvis. The obtained specimen's histological analysis revealed histiocytes and a few large cells producing granulomas without neoplastic features. The colonic biopsy's Löwenstein-Jensen medium culture revealed development of the Mycobacterium TB complex. After receiving therapy for two months with rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by four months with rifampicin and isoniazid, the patient had significantly improved. The current case serves as an example of the difficulty in diagnosing GI TB. The lack of symptoms and occasionally false-positive imaging results reinforce the necessity for increased clinical suspicion.

Diagnostic challenge of tuberculosis in systemic lupus erythematosus: a case report and literature review.

Patients with systemic lupus erythematosus (SLE) are at increased risk of tuberculosis (TB) infection due to immune dysfunction and immunosuppressive therapy. We present a case study of a 40-year-old woman with systemic lupus erythematosus (SLE). Initially, she was diagnosed with a lupus flare based on her clinical symptoms and laboratory results. However, upon further investigation, positive polymerase-chain reaction results for M. tuberculosis in the cerebrospinal fluid and lung parenchymal changes on chest computed tomography scan were indicative of TB infection. There was initial uncertainty regarding whether TB had triggered a flare-up of SLE or if TB was merely mimicking the symptoms of a SLE flare-up. However, as increasing the prednisolone dose did not have a positive effect and the patient's condition improved significantly with anti-TB treatment alone, it became clearer that the deterioration observed upon admission was primarily due to TB progression rather than an SLE flare-up. Additionally, we review the current literature on TB and SLE, including risk factors, diagnostic challenges, and treatment considerations, highlighting the importance of considering TB infection in patients with SLE who present with overlapping manifestations. Prompt diagnosis and treatment are essential for improving outcomes in these patients.

Stridor in Tuberculosis and COVID-19 Coinfection

Abstract As the SARS-CoV-2 pandemic continues to affect millions across the globe, the risk of coinfection with tuberculosis (TB) threatens patients' health and challenges our diagnostic capabilities. Here, we present a case of TB with pulmonary and laryngeal involvement complicated by coinfection with COVID-19. This case illustrates the importance of laboratory and imaging findings to differentiate between COVID-19 and TB and explores the potential for steroid use in laryngeal TB.

Pulmonary tuberculosis risks and challenges

Pulmonary Tuberculosis (PTB) is an airborne bacterial infection that can be deadly if not treated. PTB is most common in developing countries, ecologically problematic, where it kills about 1 million people each year. Pulmonary tuberculosis is a dreaded disease that can have a devastating impact on its victims. Tuberculosis is a serious respiratory infection caused by the bacterium Mycobacterium tuberculosis. It commonly affects the lungs but can also affect other parts of the body, such as the kidney, spine and brain. This review article discusses the PTB risks and challenges word wide. The global burden of TB remains high, with approximately one-third of the world's population being infected with the bacterium. Overall, more needs to be done to improve the management of TB worldwide in order to ensure that no person is left to suffer from the devastating effects of this disease.

CRISPR-Based Diagnostics: A Potential Tool to Address the Diagnostic Challenges of Tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which infects more than 23% of the world’s population. With the emergence of drug-resistant TB (DR-TB) and latent TB infection (LTBI), rapid diagnosis of DR-TB and LTBI has become a challenge for the prevention and control of TB. Herein, we highlight these challenges and discuss emerging clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics in TB detection. Currently, the clinical diagnosis of M. tuberculosis infection mainly depends on pathogenic and molecular biological methods, including sputum smear, sputum culture, and Xpert. Although CRISPR-based diagnostics have not been applied to the clinical diagnosis of TB, they have shown exciting preponderances in TB diagnosis compared with traditional methods, including higher sensitivity, less sample input, and shorter turnaround time. CRISPR-based diagnostics represent a potential tool to address the challenges and natural weaknesses associated with traditional TB diagnosis methods. Based on the currently available data, we suggest that future CRISPR-based TB diagnostics should be developed in the direction of automation, modularization, diversification, and intelligence. By combining the CRISPR platform with various systems, such as microfluidic chips, droplet microfluidics, electrochemical techniques, and optical systems, the specificity and sensitivity of TB diagnosis may be revolutionized.

Development and Application of a Multidrug-Resistant Tuberculosis Case Management System - Yunnan Province, China, 2017-2020.

IntroductionTreatment and case management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge in tuberculosis (TB) control and prevention. This pilot study aims to apply and test a new electronic information system in order to help bolster case management of MDR-TB.MethodsThe MDR-TB Case Management System (CMS) was developed and piloted in the Yunnan Tuberculosis Clinical Center (TCC) in 2017. Next, 5 sites in Yunnan were randomly selected and sampled as pilots in 2018. The real-time regular follow-up rate (RFUR) was calculated for pilot sites. Loss to follow-up (LTFU) rates of MDR-TB treatment cohorts between pilot and non-pilot sites were compared by a chi-square test. LTFU for MDR-TB treatment cohorts was then assessed by univariate and multivariate binary logistic regression.ResultsThe average regular follow-up rate was 90.7% in TCC and 73.7% in five other pilot sites of Yunnan Province respectively. The average LTFU rate for pilot sites (9.0%) was lower than non-pilot sites (20.6%, P<0.01). The risk of LTFU during MDR-TB treatment reduced 61.7% in CMS pilot cases (adjusted odds ratio: 0.38, 95% confidence interval: 0.23–0.60) compared with non-pilot cases.ConclusionsAs a significant supplement to the Tuberculosis Information Management System, the CMS strengthened the collection, analysis, and utilization of strategic information for MDR-TB cases. The system improved case management by embedding it as a tool of the Comprehensive Supportive Care service model.

Protective effects of an ethanolic leaf extract from Ficus capensis against Phenylhydrazine induced anaemia in Wistar rats

Introduction: Ficus capensis has been used in traditional medicine to treat anaemia, tuberculosis, convulsion, pains, wounds, respiratory disorders, and other health challenges. This study investigated the effect of F. capensis ethanolic leaf extract in phenylhydrazine (PHZ)-induced anaemia in Wistar rats. Methods: Induction of anaemia was done by intraperitoneal administration of PHZ (40 mg/kg for 48 hours). A normal group and an anaemic group were treated daily with a single dose of 20 mL/kg of distilled water and considered as control and anaemic (non-treated) groups. Then, the remaining groups were treated with 100, 200, and 400 mg/kg of ethanol extract of F. capensis leaves for 21 days, respectively. Blood samples from the rats were run in three batches of baseline, post anaemia induction, and post-treatment. Phytochemical screening and acute toxicity tests of the extract were also carried out following standard procedures. Results: The results showed a consistent significant increase in haematological parameters among various experimental groups. Haemoglobin (Hb), red blood cell (RBC) count, mean corpuscular volume (MCV), packed cell volume (PCV), mean cell haemoglobin (MCH) and Mean cell haemoglobin concentration (MCHC) values of treated rats were significantly increased compared to the anaemic control. The secondary metabolites of leaf extract were alkaloids, saponins, tannins, steroids, flavonoids, phenols, and reducing sugar, while the acute toxicity test was found to be non-toxic at 5000 mg/kg in rats. Conclusion: The ethanol leaf extract of F. capensis might provide an alternative cure for anaemia and boosts blood count.

Comparison of two mycobacterial strains in performance of the whole blood mycobacterial growth inhibition assay in Indian children

A major challenge in tuberculosis is identifying correlates of a protective immune response. The Mycobacterial Growth Inhibition Assay (MGIA) is a functional assay providing an integrated measure of the host immune response to mycobacteria. However, its feasibility is limited by reliance on biosafety level 3 facilities, and its performance has not been widely evaluated in TB-endemic settings. Here, we compared two mycobacterial strains (M. tuberculosis H37Rv versus attenuated M. bovis BCG) in the performance of whole-blood MGIA in 30 TB-exposed children (median age 2 years) in Chennai, India. The time-to-positivity in both assays was similar (5.7 days vs 6 days) and the mycobacterial growth of M. tuberculosis H37Rv and M. bovis BCG were correlated (r = 0.64, p<0.0001). In Bland-Altman analysis, the bias was −0.54 days (95% limit of agreement −2.08, 0.99). Collectively, our results indicate that M. tuberculosis H37Rv can be substituted with the less virulent M. bovis BCG strain to improve feasibility of the MGIA assay, particularly in low-income settings.

Dehydroquinate Synthase Directly Binds to Streptomycin and Regulates Susceptibility of Mycobacterium bovis to Streptomycin in a Non-canonical Mode

Antimicrobial resistance (AMR) represents one of the main challenges in Tuberculosis (TB) treatment. Investigating the genes involved in AMR and the underlying mechanisms holds promise for developing alternative treatment strategies. The results indicate that dehydroquinate synthase (DHQS) regulates the susceptibility of Mycobacterium bovis BCG to first-line anti-TB drug streptomycin. Perturbation of the expression of aroB encoding DHQS affects the susceptibility of M. bovis BCG to streptomycin. Purified DHQS impairs in vitro antibacterial activity of streptomycin, but did not hydrolyze or modify streptomycin. DHQS directly binds to streptomycin while retaining its own catalytic activity. Computationally modeled structure analysis of DHQS–streptomycin complex reveals that DHQS binds to streptomycin without disturbing native substrate binding. In addition, streptomycin treatment significantly induces the expression of DHQS, thus resulting in DHQS-mediated susceptibility. Our findings uncover the additional function of DHQS in AMR and provide an insight into a non-canonical resistance mechanism by which protein hijacks antibiotic to reduce the interaction between antibiotic and its target with normal protein function retained.

Tuberculosis challenges: Resistance, co-infection, diagnosis, and treatment.

Early diagnosis of tuberculosis (TB), followed by effective treatment, is the cornerstone of global TB control efforts. An estimated 3 million cases of TB remain undetected each year. Early detection and effective management of TB can prevent severe disease and reduce mortality and transmission. Intrinsic and acquired drug resistance of Mycobacterium tuberculosis (MTB) severely restricted the anti-TB therapeutic options, and public health policies are required to preserve the new medications to treat TB. In addition, TB and HIV frequently accelerate the progression of each other, and one disease can enhance the other effect. Overall, TB-HIV co-infections show an adverse bidirectional interaction. For HIV-infected patients, the risk of developing TB disease is approximately 22 times higher than for persons with a protective immune response. Analysis of the current TB challenges is critical to meet the goals of the end TB strategy and can go a long way in eradicating the disease. It provides opportunities for global TB control and demonstrates the efforts required to accelerate eliminating TB. This review will discuss the main challenges of the TB era, including resistance, co-infection, diagnosis, and treatment.