A ten-year experience of musculoskeletal tuberculosis at a tertiary care hospital in South India.

Background: The delayed identification and management of musculoskeletal tuberculosis (MSTB) poses substantial health challenges and leads to significant morbidity. This study aimed to collate ten years of hospital data and provide valuable insights into the clinical, diagnostics, and outcomes of the patients diagnosed with MSTB. Methods: A retrospective study was undertaken to review clinic records from 2013 to 2022 for all individuals diagnosed with MSTB in a tertiary care hospital in South India. Results: Over a decade, 400 cases of MSTB were diagnosed, revealing 57 % males and 43 % females with a mean age of 43.2 ± 18.9 years. Spinal TB constituted 72 % of cases, with the most common involvement of thoracic vertebrae (50.9 %). Extra-spinal MSTB accounted for 28 %, prevalent more in the pediatric age group (p < 0.05). Surgical intervention was required for 80 % of spinal TB cases and 58 % of extra-spinal MSTB cases. The average follow-up duration was two years, with 73 % completing treatment. Unfortunately, seven patients died, and three experienced relapse. Conclusion: Spinal TB is the most common type of MSTB and is predominant in young and middle-aged adults, while extra-spinal MSTB is more frequently observed in children. Where use of MRI facilitates early detection of spinal TB; histopathological and microbiological examination confirm the diagnosis. Combining anti-tubercular drugs with modern surgical approaches is essential for obtaining favorable outcomes and improving the quality of life of such patients. It is crucial to have advanced and affordable diagnostic facilities, along with increased public awareness, to reinforce tuberculosis control strategies.

Impact of Whole-Genome Sequencing of Mycobacterium tuberculosis on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review.

The emergence and persistence of drug-resistant tuberculosis is a major threat to global public health. Our objective was to assess the applicability of whole-genome sequencing (WGS) to detect genomic markers of drug resistance and explore their association with treatment outcomes for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). METHODS: Five electronic databases were searched for studies published in English from the year 2000 onward. Two reviewers independently conducted the article screening, relevant data extraction, and quality assessment. The data of the included studies were synthesized with a narrative method and are presented in a tabular format. RESULTS: The database search identified 949 published articles and 8 studies were included. An unfavorable treatment outcome was reported for 26.6% (488/1834) of TB cases, which ranged from 9.7 to 51.3%. Death was reported in 10.5% (194/1834) of total cases. High-level fluoroquinolone resistance (due to gyrA 94AAC and 94GGC mutations) was correlated as the cause of unfavorable treatment outcomes and reported in three studies. Other drug resistance mutations, like kanamycin high-level resistance mutations (rrs 1401G), rpoB Ile491Phe, and ethA mutations, conferring prothionamide resistance were also reported. The secondary findings from this systematic review involved laboratory aspects of WGS, including correlations with phenotypic DST, cost, and turnaround time, or the impact of WGS results on public health actions, such as determining transmission events within outbreaks. CONCLUSIONS: WGS has a significant capacity to provide accurate and comprehensive drug resistance data for MDR/XDR-TB, which can inform personalized drug therapy to optimize treatment outcomes.

The altered sputum microbiome profile in patients with moderate and severe COPD exacerbations, compared to the healthy group in the Indian population.

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls. Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1<80% predicted) and severe groups (FEV1<50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson's index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA>2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonasand Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group. Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.

Risk factors for the development of tuberculosis among the pediatric population: a systematic review and meta-analysis.

Pediatric tuberculosis is a major cause of mortality and morbidity in children due to high transmission, poor diagnostic tools, and various respiratory diseases mimicking TB. Identifying risk factors will provide evidence for clinicians to strongly relate their diagnosis to the associated pathology. Studies were retrieved from PubMed, Embase, and Google Scholar, systematically reviewed, and meta-analyzed for various risk factors and their association with pediatric TB. Meta-analysis depicted that four out of eleven risk factors were significant-contact with known TB cases (OR 6.42 [3.85,10.71]), exposure to smoke (OR 2.61 [1.24, 5.51]), overcrowding in the houses (OR 2.29 [1.04, 5.03]), and, poor household conditions (OR 2.65 [1.38, 5.09]). Although significant odds ratio estimates were obtained, we observed heterogeneity in the studies included.    Conclusion: The study findings demand the constant screening of risk factors such as contact with known TB cases, exposure to smoke, overcrowding, and, poor household conditions for the development of pediatric TB. What is Known: • Knowledge of the risk factors of a disease is of utmost importance in the planning and institution of its control measures. Well-established risk factors in the occurrence of TB in the pediatric group are HIV positivity, older age and close contact with a known case of TB. What is New: • In addition to what is already known; this review and meta-analysis has identified exposure to indoor smoking, overcrowding and poor household conditions as important risk factors for developing pediatric TB. • Implications of the study: The findings highlight that in addition to routine contact screening for the pediatric group, the children living in poor household conditions and getting exposed to passive indoor smoking demand more attention to prevent the development of pediatric TB.

COVID-19 and tuberculosis coinfection: A case-control study from a tertiary care center in South India.

Context: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB), are presently the major infectious diseases imposing a consequential public health threat and their coinfection has a significant impact on the outcome. Aims: To evaluate the clinical features and outcomes of COVID-19-TB coinfected cases compared to solely COVID-19-infected cases. Settings and Design: A retrospective observational study was conducted between August 1, 2020, to February 28, 2022, at a tertiary care hospital. Materials and Methods: In this case-control study, an equal number of gender-age-matched COVID-19 and TB coinfected patients and COVID-19 cases without TB were included using simple random sampling. Statistical Analysis Used: The data was analyzed using SPSS v 26. Categorical variables were compared using the Chi-square test, and an independent t-test or Mann-Whitney U test was applied for the quantitative variables in the univariate analysis. A P-value of less than 0.05 was considered significant. Results: A total of 27 patients were included in each group. Upper lobe involvement (44%) and pleural effusion (22%) were significantly more common in TB-COVID-19 cases when compared to the control group (7% and 4%, respectively; P < 0.05). Moreover, median levels of C-reactive protein and ferritin were significantly higher in TB-COVID-19 coinfection. Conclusions: Chest radiology and a higher level of certain biomarkers like C-reactive protein and ferritin can help to suspect TB in COVID-19 patients and vice-versa.

Synthesis, Molecular Docking and Evaluation of 1,3,4-Oxadiazole-Isobenzofuran Hybrids as Antimicrobial and Anticancer Agents.

In drug discovery, the hybridization of bioactive pharmacophores is a powerful tool for targeting enzymes involved in cancer and microbial cell growth. A combination of 1,3,4-oxadiazole and isobenzofuran may improve the antitumor and antimicrobial properties of the hybrid molecules. A series of hybrid molecules having 1,3,4-oxadiazole and isobenzofuran were synthesized and structural characterization was done by FT-IR, 1 H-NMR, 13 C-NMR, and mass spectrometry. Molecular docking studies were performed to investigate binding interactions of compounds with proteins (PDB NO: 2R3J and 1GII), and the results were consistent with in vitro anticancer data. All the synthesized compounds were tested for antimicrobial activity against S. aureus, E. faecalis (Gram-positive) and E. coli and P. aeruginosa (Gram-negative) bacterial strains. Among the synthesized compounds, 7a and 7b displayed good activity against the tested bacterial strains. Also, compounds were tested for their anti-tumor activity against breast cancer (MCF-7) and colon cancer (HCT-116) cell lines via SRB assay. In comparison to doxorubicin (1.14 µM), hybrids 7e (4.32 µM), 7f (4.15 µM), 7g (4.66 µM), and 7h (4.83 µM) demonstrated comparable IC50 value against the HCT 116 cell line.

Tubercular lymphadenitis in the 21st century: A 5-Year single-center retrospective study from South India.

Background: Tubercular lymphadenitis (TBLN) remains the most frequent manifestation for extrapulmonary TB despite advancements in diagnostics and management over the years. Our study intends to explore five-year trend of TBLN in a tertiary care centre from south India, and aims to study clinico-demographic and diagnostic factors in the management of TBLN. Methods: All the adult patients (≥18 years) diagnosed and confirmed for TB lymphadenitis between January 2015 to December 2019 were retrospectively evaluated. Demographic factors, clinical manifestations, and different diagnostic approaches used in the management of TBLN were analysed using SPSS ver. 16. Results: A total of 164 patients with confirmed TBLN were included. Patients aged 18-45 years were the most affected (63.41%) with female dominancy. The most affected lymph nodes were cervical lymph nodes (84.1%) presenting with single palpable enlarged lymph node (80.5%). Majority (78.7%) of the lymph nodes were non-matted and 68.9% of enlarged lymph nodes were >3cm size. Excisional biopsy was performed for the majority of the patients 99 (60.4%) and 60.4% of the cases were managed with a combination of surgical excision and anti-tubercular treatment (ATT). Conclusions: The declining trend of TBLN observed in this study highlights the outcome of good public health policies; however, young females and high-risk groups like HIV infected or AIDS (affected more in the study) demand further attention. Overall, the advanced diagnostic tools along with surgical management and ATT can lead us to earlier diagnosis and successful treatment outcomes.

Challenges Perceived by Health Care Providers for Implementation of Contact Screening and Isoniazid Chemoprophylaxis in Karnataka, India.

Background: In India, challenges in pediatric TB contact screening and chemoprophylaxis initiation are still underexplored. Elucidating these challenges will help in better implementation of the programme at the grass-roots level thereby helping in early detection of pediatric cases and timely initiation of preventive therapy. This study aimed at exploring the challenges faced by the health care provider in contact screening and chemoprophylaxis initiation implementation of the pediatric household contacts. Methods: A qualitative study was conducted in the districts of Bengaluru and Udupi and in-depth interviews of key participants were adopted to explore the challenges. Qualitative data analysis was done after developing transcripts by generating themes and codes. Results: The key challenges were identified as stigma towards the disease, migrant patients with changing address, difficulty in sample collection, anxiety among parents due to long duration of the prophylactic treatment and adherence to IPT is not well documented, inadequate transportation from rural areas, and the ongoing COVID-19 pandemic. Conclusions: It is important for the National TB programme to address these challenges efficiently and effectively. Innovative solutions, feasible engagements, and massive efforts are to be taken by the programme to improve contact screening and isoniazid chemoprophylaxis implementation.

The aftermath of COVID-19 pandemic on the diagnosis of TB at a tertiary care hospital in India.

BACKGROUND: The recent COVID-19 pandemic became a looming catastrophe over global public health and severely disrupted essential healthcare services like tuberculosis (TB). This study estimated the impact of the COVID-19 in the diagnosis of TB, a microbiology laboratory-based overview. METHOD: This ambispective observational study was conducted at the Department of Microbiology in a tertiary care hospital in South Karnataka from January 2019 to December 2020. A standardized data collection sheet was prepared to collect the month-wise total number of suspected TB and confirmed TB samples. Data were analyzed using EZR 3.4.3 (R, open-source). Categorical variables were expressed in frequency and percentage. The Chi-square test was performed to test the difference in proportions and p < 0.05 indicated statistical significance. RESULTS: In this study, a significant drop was observed in suspected TB specimens in 2020 compared to 2019, i.e. 54.8% for microscopy, along with 34.2% and 49.7% for Xpert MTB/RIF and MGIT culture respectively. Also, a sharp decline in confirmed TB samples was noted in 2020 with 49%, 43.8%, and 59.7% reduction with microscopy, Xpert MTB/RIF, and MGIT culture respectively, compared to 2019. Another major finding from this study reveals the PTB: EPTB proportion changed from 2.7:1 in 2019 to 2.1:1 in 2020, divulging an overall increase in EPTB sample proportion in 2020 (p = 0.0385). CONCLUSION: The COVID-19 pandemic adversely impacted the TB diagnostic services, resulting in a significant reduction of active TB case detection. It highlights an urgent need to revise the strategies to control and eliminate TB in this hour of the pandemic crisis.