Identifying quantitative sncRNAs signature using global sequencing as a potential biomarker for tuberculosis diagnosis and their role in regulating host response.

OBJECTIVES: The study aimed to identify a quantitative signature of circulating small non-coding RNAs (sncRNAs) as a biomarker for pulmonary tuberculosis disease (active-TB/ATB) and explore their regulatory roles in host-pathogen interactions and disease progression. METHODS: We conducted a cross-sectional study recruiting subjects diagnosed with active-TB (drug-sensitive and drug-resistant) and healthy controls. Sera samples were collected and utilized for preparing small RNA libraries. Quantitative patterns of circulating sncRNAs (miRNAs, piRNAs and tRFs) were identified via high-throughput sequencing and DeSeq2 analysis and validated in independent active-TB cohorts. Functional knockdown for two selected miRNAs were also performed. RESULTS: A diagnostic signature of four sncRNAs for both drug-sensitive and drug-resistant active-TB cases was validated, exhibiting an AUC of 0.96 (95% CI: 0.937-0.996, p < 0.001) with 86.7% sensitivity (95% CI: 0.775-0.932) and 91.7% specificity (95% CI: 0.730-0.990) in ROC analysis. Functional knockdown demonstrated regulatory roles of hsa-miR-223-5p and hsa-miR-10b-5p in Mycobacterium tuberculosis (Mtb) growth and pro-inflammatory cytokine expression (IL-6 and IL-8). CONCLUSION: The study identified a diagnostic tool utilizing a signature of four sncRNAs with high specificity and sensitivity, enhancing our understanding of sncRNAs as ATB diagnostic biomarker. Additionally, hsa-miR-223-5p and hsa-miR-10b-5p demonstrated potential roles in Mtb pathogenesis and host-response to infection.

Situation Analysis of Early Implementation of Programmatic Management of Tuberculosis Preventive Treatment among Household Contacts of Pulmonary TB Patients in Delhi, India.

Tuberculosis Preventive Treatment (TPT) is a powerful tool for preventing the TB infection from developing into active TB disease, and has recently been expanded to all household contacts of TB cases in India. This study employs a mixed-methods approach to conduct a situational analysis of the initial phase of TPT implementation among household contacts of pulmonary TB patients in three districts of Delhi, India. It was completed using a checklist based assessments, care cascade data, and qualitative analysis. Our observations indicated that organizational structure and planning were established, but implementation of TPT was suboptimal with issues in drug availability and procurement, budget, human resources, and training. Awareness and motivation, and shorter regimen, telephonic assessment, and collaboration with NGOs emerged as enablers. Apprehension about taking TPT, erratic drug supply, long duration of treatment, side effects, overburden, large population, INH resistance, data entry issues, and private provider reluctance emerged as barriers. The study revealed potential solutions for optimizing TPT implementation. It is evident that, while progress has been made in TPT implementation, there is room for improvement and refinement across various domains.

Adverse drug reactions in children and adolescents on daily antitubercular regimen: An observational longitudinal study.

OBJECTIVES: Subsequent to introduction of daily fixed dose combination (FDC) regimen with increased dosages and inclusion of ethambutol in continuation phase of antitubercular therapy (ATT) in India, this study was done to evaluate adverse drug reactions (ADRs) in children and adolescents. METHODS: Longitudinal observational study conducted in tertiary teaching hospital. Children (1 month-18 year), with newly diagnosed drug sensitive tuberculosis, started on daily FDC regimen of ATT, were included. Participants were followed up at 2 weeks, 8 weeks and 6 months. Division of AIDS (DAIDS) severity grading and World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment was done. RESULTS: In 99 participants, 29 experienced ADRs. Most commonly ADRs involved hepatobiliary (11.1%) and gastrointestinal (8.1%) systems. Grade 3 severity noted in 35.5% ADRs. Certain causality classified in 19.3%. Presence of ADRs was significantly higher in participants with vs without malnutrition [40.5% vs 21.1% (p = 0.036)]. Tendency for more severe ADRs noted in participants with vs without malnutrition [Grade 3 ADRs out of all ADRs: 64.7% vs 0% (p < 0.001)]. CONCLUSION: Incidence and severity of ADRs has increased after introduction of daily FDC of ATT. Most common ADR observed were hepatobiliary. Malnutrition and less weight for age were risk factors for occurrence and severity of ADRs.

Implementation of tuberculosis preventive therapy with INH-Rifapentine (3HP) for latent tuberculosis infection management in household tuberculosis contacts in India: A prospective study.

OBJECTIVE: The primary objective of this study was to ascertain the acceptance, initiation, implementation and treatment completion rates of tuberculosis (TB) preventive therapy (TPT) using 3HP (INH-Rifapentine) among household contacts of microbiologically confirmed drug sensitive TB cases on anti-tubercular treatment under programmatic real-world settings. The secondary objectives were to estimate the prevalence and predictors of latent TB infection (LTBI) in household contacts of the index TB cases. We also ascertained the safety profile of the 3HP TPT regimen in the household contacts. METHODS: This prospective observational study was conducted at 10 TB chest clinics in Delhi, India during 2022-2023. Household contacts aged 14 and older who tested positive for TB infection on a Tuberculin Skin test were initiated on the 3HP regimen. Logistic regression was performed by including statistically significant independent variables in multiple prediction models. p < 0.05 was considered statistically significant. STATA, version 15.1, was used to compute all analyses. RESULTS: A total of 1067 (84.68%) eligible contacts of microbiologically confirmed, drug sensitive TB cases underwent screening with tuberculin skin test (TST), 614 (95.6%) LTBI positive contacts accepted the initiation of TPT, and 564 (91.8%) of those initiated on TPT completed the treatment. The major reason for refusal of screening was the lack of perception of risk of TB disease due to asymptomatic status. The prevalence of LTBI positivity through TST was 61.5% (95% CI, 58.5%, 64.4%). Adverse events were reported by 195 (31.8%) contacts initiated on 3HP of which 20 participants discontinued TPT. None of the sociodemographic factors showed a significant association with LTBI positivity (except age) or TPT completion rates. CONCLUSION: LTBI management with 3HP is feasible among adolescent and adult household contacts in India with high rates of adherence from initiation until treatment completion. The maximum attrition of participants occurred at the time of screening for LTBI using TST.

Correlating clinical breakpoint concentration of moxifloxacin with gyrA mutations using the GenoType MTBDRsl assay Version 2.0.

INTRODUCTION: Widespread use of Fluoroquinolones (FQs) has led to the development of its resistance in clinical isolates of Mycobacterium tuberculosis. However, in Mycobacterium tuberculosis, phenotypic resistance to FQs has been shown to be heterogeneous, ranging from low-level resistance to high-level resistance. This stratification in resistance has important implications for the inclusion of moxifloxacin (Mfx) in the treatment regimen. The World Health Organization recommends the use of GenoType MTBDRsl assay as the initial test for detecting resistance conferring mutations (both high and low) to FQs in patients with confirmed MDR-RR TB. The present study was conducted to explore the relationship of MTBDRsl Version 2.0 detected mutations in gyrA gene and genotypic DST of Mfx at WHO defined Clinical Breakpoint (CB). MATERIALS AND METHODS: A total of 200 sputum samples from Confirmed MDR/RR TB patients were included in this study. All of these samples had mutations conferring resistance to FQ confirmed by GenoType MTBDRsl assay. These samples were further subjected to Phenotypic DST against moxifloxacin using the Bactec MGIT-960 system. RESULTS: All of the 200 representative FQ resistant isolates had mutations in gyrA gene only with no detectable mutation in gyrB gene. 109 (54.5%) of the isolates had mutations associated with high-level increase in MIC while 91 (45.5%) isolates had mutations associated with low-level increase in MIC. Phenotypic DST of these 200 isolates against Mfx at CB (1.0µg/ml) revealed that of the 109 isolates with mutations associated with high-level increase in MIC and expected to be resistant at CB, only 34 (31.2%) were resistant and the remaining 75 (68.8%) were sensitive. CONCLUSION: Moxifloxacin is an important drug in the regimen for treating Drug-resistant TB and the decision to exclude this drug from the regimen should not be taken merely on the basis of mutational patterns. It should rather be taken after considering the combined results of mutational analysis and phenotypic DST.

National TB elimination programme - What has changed.

BACKGROUND: Before the start of Coronavirus (COVID-19) pandemic, TB was the leading cause of death due to a single infectious agent, ranking well above HIV/AIDS. Almost one-fourth of the world's population is infected with M. tuberculosis. TB is curable and preventable. About 85% of people who develop TB can be successfully treated with drug regimens of 6 months. Universal health coverage (UHC) is necessary to ensure that all those with the disease can access these treatments. Research breakthroughs (e.g., newer rapid diagnostic techniques, drugs, newer vaccine) are needed to rapidly reduce the number of new cases each year (TB incidence) worldwide. OBJECTIVE: Changes in the National TB Elimination Programme since its inception. CONTENT: The Government of India launched the "National TB Programme" in 1962 as District TB Centre model involved with BCG vaccination and TB treatment to fight tuberculosis, a major public health problem. The tuberculosis control programme has come a long way since then and has undergone major changes over the past few years The Ministry of Health and Family Welfare has developed the "National Strategic Plan" for Tuberculosis Elimination (2017-25) which encapsulates the bold and innovative steps required to eliminate TB in India by 2025, five years ahead of the global targets. By 2020 it was clear that the NSP- 2017-25 will not be able to meet these objectives, so another new NSP India 2025 had been launched in 2020. India has been actively involved in TB control activities for more than 50 years now. TB still continues to be a severe health problem in India. The country is now better prepared to tackle TB than before. It now has advanced and effective interventions and technologies for diagnosis, treatment and care of TB cases.

Utility of a Clinical Scoring System (Bandim TB Score and Karnofsky Performance Score) to Assess Mycobacterial Burden in Terms of Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) Cycle Threshold Values Among Pulmonary TB Patients.

AIM: Tuberculosis (TB) continues to be a global public health problem. Physicians fail to clearly interpret cycle threshold (Ct) values as a measure of mycobacterial burden due to the paucity of literature correlating Ct values with the clinical scoring. This study aims to correlate the clinical scoring parameters (Bandim TB score and Karnofsky Performance score (KPS)) with Ct values obtained by Cartridge-Based Nucleic Acid Amplification Test (CBNAAT). MATERIALS AND METHODS: The study spanned from November 2019 to October 2021, during which a total of 40 cases were recruited. These cases were identified as pulmonary TB patients based on Ziehl-Neelsen staining for acid-fast bacilli and/or the GeneXpert MTB/RIF assay. Bandim TB scores and KPSs were recorded using standardized questionnaires. RESULTS: There was a strong negative correlation between Bandim TB score and Ct value (mean), and this correlation was statistically significant (rho = -0.82, p < 0.001). There was a moderate positive correlation between KPS and Ct value (mean), and this correlation was statistically significant (rho = 0.57, p < 0.001). CONCLUSION: No literature has compared Bandim TB score and KPS with the Ct values obtained by CBNAAT for pulmonary TB. Thus, the knowledge on the proper utilization of CBNAAT cycle threshold values and its correlation with clinical scoring parameters will help clinicians in the early identification and prompt initiation of appropriate treatment.

Effectiveness of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis at various stand-alone laboratories in Delhi.

BACKGROUND: Globally, EPTB accounts for 15% of the notified incident TB cases. Laboratory confirmation of EPTB is challenging and majority of the cases remain undetected for a longer time. A major breakthrough in the diagnosis of EPTB was the introduction of nucleic acid amplification tests (NAAT). One such test-the Xpert MTB/RIF assay also known as Cartridge based nucleic acid amplification test (CBNAAT) was endorsed by the Scientific and Technical Advisory Board of the WHO for the diagnosis of Tuberculosis. The present study was conduct to evaluate the outcome of various extrapulmonary samples tested in the year 2019 at different standalone NAAT laboratories in Delhi. MATERIALS AND METHODS: A total of 20,238 samples consisting mainly of Pus (21.77%), Cerebrospinal fluid (CSF) (14.96%), Biopsies (13.87%), Pleural fluid (10.49%), Lymph node aspirations (FNAC aspirates) (6.75%), synovial fluid (0.54%) and gastric aspirates (26.4%) tested at 22 standalone NAAT laboratories were included in this study. RESULTS: Mycobacterium tuberculosis was detected in 3496 samples and resistance to rifampicin was detected in 329 of the samples. The overall yield of all the specimens combined was 17.2%. Highest yield was seen in Lymph nodes aspirates (FNAC) (36.0%), followed by pus (35.4%), tissues (15.7%), synovial fluid (13.5%), Endometrial tissues (10.7%), Pleural fluid (9.5%), Gastric aspirates (9.4%) and CSF (6.5%). The lowest yield was seen in Cavitary fluids (6.2%). CONCLUSION: The results of this study highlight the usefulness of Xpert MTB/RIF assay in the diagnosis of EPTB. In particular, this assay proved to be of great utility while testing pus samples, tissue samples and lymph node FNACs.

"DOST" Model to Link and Support Drug Resistant TB Patients From Private Sector: An Experience From Delhi, India.

Background: The National TB Elimination Programme (NTEP) has quite successfully involved private sector for referral of presumptive drug resistant TB (DR-TB) patients for molecular testing and referral for DR-TB management. There was a challenge as all the referred patients were not reaching to the facilities. A "DOST" intervention model was implemented to strengthen the patient care pathway. We conducted this study to describe the patient care cascade, the clinico-demographic characteristics of patients linked to the treatment and to estimate the mean turn-around time for drug resistant TB care services. Methods: It is a cross-sectional study conducted at New Delhi during the period July 2019-December 2020 under programmatic settings. Results: A total of 9,331 patients were subjected to CB-NAAT test and 382 (4%) were found to be resistant for rifampicin and 231 (76%) were initiated on treatment in the public sector under NTEP. Conclusion: The DOST intervention model developed to link the DR-TB patients from private sector to the public sector DR-TB centers is found to be efficient and effective.

Evaluating the efficacy of stool sample on Xpert MTB/RIF Ultra and its comparison with other sample types by meta-analysis for TB diagnostics.

Precise and timely detection of tuberculosis (TB) is crucial to reduce transmission. This study aims to assess the accuracy of Xpert MTB/RIF Ultra on stool samples and systematically review the performance of Xpert MTB/RIF Ultra with different sample types by meta-analysis. Stool samples of smear-negative pulmonary TB (PTB), cervical lymph node TB, and abdominal TB patients were tested on the Xpert MTB/RIF Ultra system. Meta-analysis was performed on a set of 44 studies. Data were grouped by sample type, and the pooled sensitivity and specificity of Xpert MTB/RIF Ultra were calculated. The sensitivity of Xpert MTB/RIF Ultra with stool samples was 100% for smear-negative PTB, 27.27% for cervical lymph node TB, and 50% for abdominal TB patients, with 100% specificity for all included TB groups. The summary estimate for all PTB samples showed 84.2% sensitivity and 94.5% specificity, and EPTB samples showed 88.6% sensitivity and 96.4% specificity. Among all sample types included in our meta-analysis, urine showed the best performance for EPTB diagnosis. This pilot study supports the use of stool as an alternative non-invasive sample on Xpert MTB/RIF Ultra for rapid testing, suitable for both PTB and EPTB diagnosis.

Latent Tuberculosis Infection Diagnosis among Household Contacts in a High Tuberculosis-Burden Area: a Comparison between Transcript Signature and Interferon Gamma Release Assay.

Diagnosis of latent tuberculosis infection (LTBI) using biomarkers in order to identify the risk of progressing to active TB and therefore predicting a preventive therapy has been the main bottleneck in eradication of tuberculosis. We compared two assays for the diagnosis of LTBI: transcript signatures and interferon gamma release assay (IGRA), among household contacts (HHCs) in a high tuberculosis-burden population. HHCs of active TB cases were recruited for our study; these were confirmed to be clinically negative for active TB disease. Eighty HHCs were screened by IGRA using QuantiFERON-TB Gold Plus (QFT-Plus) to identify LTBI and uninfected cohorts; further, quantitative levels of transcript for selected six genes (TNFRSF10C, ASUN, NEMF, FCGR1B, GBP1, and GBP5) were determined. Machine learning (ML) was used to construct models of different gene combinations, with a view to identify hidden but significant underlying patterns of their transcript levels. Forty-three HHCs were found to be IGRA positive (LTBI) and thirty-seven were IGRA negative (uninfected). FCGR1B, GBP1, and GBP5 transcripts differentiated LTBI from uninfected among HHCs using Livak method. ML and ROC (Receiver Operator Characteristic) analysis validated this transcript signature to have a specificity of 72.7%. In this study, we compared a quantitative transcript signature with IGRA to assess the diagnostic ability of the two, for detection of LTBI cases among HHCs of a high-TB burden population; we concluded that a three gene (FCGR1B, GBP1, and GBP5) transcript signature can be used as a biomarker for rapid screening. IMPORTANCE The study compares potential of transcript signature and IGRA to diagnose LTBI. It is first of its kind study to screen household contacts (HHCs) in high TB burden area of India. A transcript signature (FCGR1B, GBP1, & GBP5) is identified as potential biomarker for LTBI. These results can lead to development of point-of-care (POC) like device for LTBI screening in a high TB burdened area.

Utility of stool CBNAAT in the diagnosis of pediatric pulmonary tuberculosis in India.

BACKGROUND: India houses 27% of the tuberculosis cases worldwide. Pediatric tuberculosis accounts for 11% cases worldwide. Microbiological confirmation of diagnosis is difficult in children. We aimed to study the proportion of Stool CBNAAT (Cartridge Based Nucleic Acid Amplification Test) and GA CBNAAT positive cases among the presumptive cases of tuberculosis in children and assess diagnostic utility of the Stool CBNAAT in comparison to GA CBNAAT and culture. METHODS: Ours was a cross sectional study. 75 children, aged 6 months to 12 years who were presumptive cases of pulmonary tuberculosis and who were unable to expectorate, were enrolled. Gastric aspirate and stool samples were obtained and CBNAAT and culture was done. Results of stool CBNAAT were compared with GA CBNAAT and culture. RESULTS: Of the 75 children enrolled, 28 were started on antitubercular therapy, 12 of whom were microbiologically confirmed and 16 were started on clinical grounds. Overall, 10 (13.3%) and 11 (14.6%) were positive by Stool CBNAAT and GA CBNAAT respectively. GA CBNAAT and Stool CBNAAT were found to have near perfect agreement (Cohen's kappa 0.834). Stool CBNAAT had sensitivity and specificity of 73% and 97% as compared to culture. CONCLUSIONS: Stool CBNAAT may be used for bacteriological confirmation of pediatric pulmonary tuberculosis. It was found to have a high degree of concordance with the conventionally used GA CBNAAT. This test would be helpful in endemic countries where there is a dearth of trained staff, especially in the periphery, to obtain gastric aspirate. Discomfort associated with sampling would be avoided.

The intention to receive tuberculosis preventive therapy in adult household contacts of pulmonary TB patients in Delhi, India.

INTRODUCTION: The integration of newer tuberculosis preventive therapy regimens, which have shorter treatment duration, simpler dosing requirements, and improved safety profile, is being considered within India's national tuberculosis elimination program. However, a potential operational challenge in the successful rollout of the expanded TPT plan is the extent of its acceptability in adult household contacts of pulmonary tuberculosis patients due to possibility of lower risk perception and suboptimal perceived benefit. This study was conducted to determine the intention to accept Tuberculosis Preventive Therapy among adult household contacts of pulmonary tuberculosis patients in Delhi, India. METHODOLOGY: This cross-sectional study was conducted from June-November 2020 in Delhi, India. Data were collected through face to-face interviews by trained field investigations from the high-risk adult household contacts of PTB patients. RESULTS: A total of 536 household contacts including 237 (44.2%) men and 299 (55.8%) women were recruited with median (IQR) age 40 (22-52) years. Risk factors for incident tuberculosis observed in the HHCs were undernourishment (32.3%), overweight (47.8%), and diabetes comorbidity (10.6%). Most of the participants had not heard of latent TB infection (97.3%) The intention to accept tuberculosis preventive therapy was reported by 394 (73.5%) participants with an absence of symptoms (33.1%), feeling completely healthy (42.9%), and drug adverse effects (27.5%) (n=142) being primary drivers of non-intention. CONCLUSIONS: Nearly three in four HHCs without TB disease expressed willingness to accept TPT if prescribed with caveat for the social desirability bias.

Adherence to Isoniazid Preventive Therapy among children living with tuberculosis patients in Delhi, India: An exploratory prospective study.

INH Preventive Therapy (IPT) substantially reduces the risk of incidence of TB disease in pediatric household contacts of TB patients. The National TB Elimination Program (NTEP) of India prescribes a daily regimen of Isoniazid to all under-6 pediatric contacts for 6 months duration. We conducted, this exploratory prospective study (June to Nov' 2020) to assess adherence to IPT and reasons for nonadherence among child contacts of microbiologically confirmed, drug sensitive, non-PLHIV Tuberculosis patients in Delhi, India. The study outcomes included the initiation, adherence and completion of IPT. The caregivers of the child TB contacts were interviewed face to face by the field investigator. The data were entered on EpiData 3.1 and analysed with IBM SPSS 25. The INH adherence was assessed in a total of 86 household child TB contacts. IPT had been initiated in 62 (72.1%) child TB contacts of which 61 (98.4%) received INH within 1 month of starting of ATT-DOTS therapy in the index TB patient of the household. Furthermore, the failure to initiate IPT was reported by 24 (27.9%) child TB contacts. Within the cohort of child TB contacts who were not initiated with IPT, the ATT-DOTS duration in the index-TB patient was ≥5 months in 18 (75%) cases, 1-2 months in 3 (12.5%) cases, and <1 month in also 3 (12.5%) cases. Reasons for non-initiation (n = 24) were reported as refusal by the family in 12 (50%) cases mostly due to concern over side-effects of the drug, while non-provision of the drug by the DOTS provider was also observed in 12 (50%) cases. The mean (SD) INH adherence in the INH initiated cohort was 5.6 (2.0) (n = 62). Reasons for INH non-adherence were attributed to forgetfulness (n = 23, 37.1%), carelessness (n = 24, 38.7%), and intermittent stopping of the medication (n = 17, 27.4%) on the child falling sick, perceived drug side effects, and running out of drug stocks. INH non-adherence defined as at-least two missed INH doses in the previous 7 days was observed in 47 (54.7%) participants (n = 86). On bivariate analysis, none of the household sociodemographic characteristics showed any statistically significant association with the rate of INH non-adherence in the child TB contacts. The findings of the present study indicate the need to periodically assess adherence and persistence to IPT in the child TB contacts as high intermittent missed dosing rates can undermine the effectiveness of IPT in preventing incident disease.

Socio-clinico-radiological profile of smear-positive pulmonary tuberculosis patients in association with sputum conversion and baseline hsCRP levels.

Our was an observational follow-up study where the aim was to assess the baseline high-sensitivity C-reactive protein levels in 50 smear-positive pulmonary tuberculosis patients in association with socio-clinico-radiological profile and microbiological conversion. Smear and culture conversion of sputum samples at the end of intensive phase of anti-tubercular treatment were recorded. Baseline serum high-sensitivity C-reactive protein estimation was done by ELISA. Mean high-sensitivity C-reactive protein levels at baseline, smear/culture converted and delayed converters were 68.1 ± 22.2 mg/l, 66.7 ± 22.0 mg/l and 91.6 ± 6.7 mg/l, respectively; high-sensitivity C-reactive protein levels were significantly higher in delayed converters as compared to sputum converters. Significantly higher baseline high-sensitivity C-reactive protein levels were seen in patients with bilateral chest X-ray lesions, cavitations, evening rise of temperature, haemoptysis and dyspnoea as compared to those without these features. high-sensitivity C-reactive protein, being a non-specific inflammatory marker could be an adjunct tool for TB prognosis.

Pre-conference workshop on drug resistant TB - NATCON 2020.

Pre-conference workshop on Drug Resistant Tuberculosis was conducted under the banner of NATCON-2020 on 18th December 2020. The workshop covered various aspects of diagnosis including newer rapid genotypic methods, and gene sequencing. The workshop deliberated on the latest recommendations of the global and national guidelines about the management of DR-TB patients. Case scenarios focusing on the management of MDR TB and XDR TB patients were presented and the principles of making the regimen for DR-TB patients were discussed. Various aspects of shorter MDR TB regimen including bedaquiline containing shorter regimen and all oral longer regimen for DR-TB patients were also presented to the participants. The participants were also informed regarding what is in store in the near future at global and national level regarding the management of DR-TB patients. The participants included students, teaching faculty and the practicing physicians. The workshop informed the delegates on the latest recommendations of the global and national guidelines about the management of DR-TB. The detailed deliberations were very useful for the participants in their day-to-day clinical practice. The main highlights of the workshop have been mentioned below.

Spectrum of Drug Resistance in Musculoskeletal Tuberculosis.

BACKGROUND: Very few studies report resistance pattern exclusively in musculoskeletal tuberculosis (MSK-TB). METHODS: This study of 100 pus samples from patients of MSK-TB with active disease in whom Mycobacterium tuberculosis (MTB) was detected by cartridge-based nucleic acid amplification test (CBNAAT), revealed the pattern of resistance among newly diagnosed and previously treated cases. Liquid culture and drug susceptibility testing (DST) using MGIT 960 was done for 11 anti-tubercular drugs. RESULTS: Among these 100 cases; 22% were AFB positive; MGIT 960 detected MTB in 58.33% (35/60) new cases and 30.0% (12/40) previously treated cases. Five new and 10 previously treated cases had drug resistance and 12 were detected rifampicin resistance (Rif-R) by CBNAAT. Among new cases MGIT-DST detected mono-INH resistant in 2.86% (1/35), mono-STR resistant in 2.86% (1/35), MDR-TB in 5.7% (2/35) and pre-XDR in 2.9%(1/35).Among previously treated cases Rif-R was found in 10% (4/40) where MTB was not detected by MGIT and MGIT-DST detected mono-INH resistant in 8.33% (1/12); MDR-TB in 8.33% (1/12) and pre-XDR in 33.3%. There were no cases of XDR-TB. CONCLUSION: High disease burden of various type drug resistance were seen more commonly in previously treated cases and was not uncommon in new cases of MSK-TB. Both CBNAAT and DST are essential for detecting resistance pattern in MSK-TB.

The effect of a mhealth intervention on anti-tuberculosis medication adherence in Delhi, India: A quasi-experimental study.

BACKGROUND: Suboptimal adherence to anti-tuberculosis medication in patients is associated with adverse treatment outcomes including treatment failure, relapse, and emergence of drug resistance. OBJECTIVES: : We conducted the present study with the objectives of evaluating the effectiveness of a mHealth package on the medication adherence of patients with tuberculosis (TB) on antitubercular (directly observed treatment short-course [DOTS]) treatment. METHODS: We conducted Quasi-experimental study at six DOTS centers of Delhi among 220 newly diagnosed TB patients. We included adult TB patients (18 years and above) who were on DOTS therapy ≥30 days, had access to a mobile phone and were able to read messages and receive calls. We excluded patients with impaired hearing, blindness and those on non-DOTS therapy or having multidrug-resistant/extensively drug-resistant TB. Participants in the intervention group received amHealth package for 90 days. The medication adherence of the study participants was measured using Morisky, Green, and Levine Adherence Scale. RESULTS: A total of 130 men and 90 women were recruited for the study. Occupational interference and forgetfulness were the most common reasons for medication nonadherence in the patients. In the intervention group, the medication adherence to antitubercular medication (daily DOTS regimen) was 85.5% at baseline which increased to 96.4% at endline (postintervention) (P = 0.004). No significant change was observed in the control group (P = 0.328). The increase in adherence was observed across the following subgroups: age, gender, education, and Socioeconomic status. CONCLUSIONS: The mHealth intervention in TB patients was effective in improving the adherence to DOTS therapy.

Clinico-immunological profile in a case of hepatic tubercular abscess: A rare manifestation of extrapulmonary TB in an immunocompetent child.

Tubercular liver abscess is a rare entity even in an endemic area for TB. We report here a rare case of pediatric tuberculous liver abscess, the etiology of which was established using recently introduced Cartridge based nucleic acid amplification test (CBNAAT). A 7 years old male child presented with vomiting, pain abdomen and fever. Hepatomegaly was found on examination. Ultrasound of abdomen revealed two liver abscesses in the right lobe. Patient remained symptomatic even after empirical antimicrobial therapy. On diagnostic tap Gram stained smear of the pus showed polymorphs with negative culture. CBNAAT was positive for Mycobacterial tuberculosis and sensitive to rifampicin. Subjecting difficult extrapulmonary specimens to relevant microbiological investigations along with CBNAAT and other newer methods may improve diagnosis of tuberculosis in such rare cases thus leading to an early management and decrease in morbidity.