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Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

Introduction The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities.Methods Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020–October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting.Results Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30–60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6–7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03).Conclusion Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Objectives: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. Methods: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. Results: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. Conclusion: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.

Melioidosis is a complex tropical disease linked with many complications. It is increasingly diagnosed in India. The clinical mimicry of this disease with several other common causes of pneumonia has kept the clinicians in ignorance. Usually, the diagnosis and appropriate management get delayed. The organism closely resembles the common contaminant Pseudomonas and is easily misidentified in microbiology laboratories. The diagnosis is often missed because of poor diagnostic sensitivity of blood culture, the gold standard of the diagnosis. All this contributes to increased morbidity and mortality. The rampant use of high-end broad-spectrum antibiotics like ceftazidime and meropenem at suboptimal dose and duration suppresses the diagnosis without eradicating the disease, leaving the chance of recurrence from its latency even after years. As an infectious disease, the cure and prevention depend on early diagnosis and treatment. An awareness of its peculiar presentations and history can differentiate clinically and suspect the condition much easily from other mimickers of tuberculosis to sepsis. Ultimately, the prevention of melioidosis remains the critical strategy. Increasing the number of cases and intricated management of this fatal but potentially curable disease had prompted us to take up the mission of preventing the disease by spreading knowledge and awareness.

Background: Nontuberculous mycobacteria (NTM) are on the rise worldwide. The diagnosis and treatment of NTM disease create a dilemma for physicians as their clinical features often overlap with that of tuberculosis (TB). The present study aims to report a series of NTM infections presenting as suspected TB. Methods: It was a prospective observational study starting from December 2018 to January 2022. A total of 1850 suspected TB patients (pulmonary = 522 and extrapulmonary = 1328) were included in this study. Clinical features, radiological findings, microbiological diagnosis, treatment, and outcome were recorded. Clinical specimens were processed for Ziehl–Neelsen staining, GeneXpert MTB/Rif assay by cartridge-based nucleic acid amplification test, and culture. The culture-positive isolates were categorized as Mycobacterium tuberculosis complex or NTM depending on the detection of MPT64 antigen by immunochromatographic test. The NTM isolates were speciated by line probe assay using GenoType® Mycobacterium common mycobacteria kit. The criteria of the American Thoracic Society/Infectious Diseases Society of America were applied to confirm NTM disease. Results: Of 1850 suspected TB patients, NTM disease was diagnosed in 20 patients (pulmonary = 9, nonpulmonary = 11). Eight NTM cases presented as suspected drug-resistant-TB with a history of antitubercular therapy. Among pulmonary NTM cases, Mycobacterium scrofulaceum (n = 7) was the most common species followed by Mycobacterium kansasii (n = 1) and Mycobacterium intracellulare (n = 1). In nonpulmonary cases, Mycobacterium abscessus (n = 8) was involved in majority of cases followed by Mycobacterium fortuitum (n = 3). Cavitary lung disease and laparoscopic port site infections were most frequent pulmonary and non-pulmonary manifestations respectively. Conclusion: Hence, there is an urgent need for better diagnostic and drug susceptibility testing facility along with standardized treatment protocol for NTM disease.

Community-acquired Burkholderia cepacia pneumonia is uncommon. We report a 32-year-old female who was on oral erlotinib, a tyrosine kinase inhibitor, for 2 years for her lung cancer and developed community-acquired Burkholderia cepacia pneumonia, which was confirmed by blood culture. The patient improved with antibiotics.

A 37-year-old male presented with left-sided hydropneumothorax. After drainage of fluid and air from the pleural cavity, chest radiograph and computed tomography of chest showed characteristic radiological image of ruptured hydatid cyst. The diagnosis was supported by positive echinococcal serology.

Background: Patients with chronic obstructive pulmonary disease (COPD) develop acute exacerbations (AE), with varying natural history. The exacerbation is triggered by infection, leading to increased morbidity and mortality. The study on infectious aetiology of AECOPD is largely restricted to only viral or only bacterial aetiology. There are no studies from India that have investigated multiple viral, bacterial, and fungal associations from the same group of patients. This prospective study was conducted over 2 years to estimate the incidence and profile of viral infections in AECOPD patients, their coinfection with other bacterial and fungal agents, and association of the type and pattern of infective agent with the clinical severity. Materials and Methods: Seventy-four AECOPD cases were included in the study. Multiplex polymerase chain reaction was performed from nasopharyngeal swab using Fast Track Diagnostics Respiratory Pathogens 21 Plus Kit. Ziehl–Neelsen (ZN) stain, Modified ZN, and potassium hydroxide (KOH) mount were performed for Mycobacteria, Nocardia, and fungal elements. Bacterial cultures and fungal cultures were done as per the standard techniques. Serum samples were tested for Mycoplasma and Chlamydia pneumoniae immunoglobulin M enzyme-linked immunosorbent assay. Results: The number of AECOPD events involving only viral infection, only bacterial infection, bacterial–viral coinfection, and no infection were 43 (58.1%), 32 (43.2%), 20 (27%), and 19 (25.7%), respectively. Influenza A virus was the most common virus (22/43, 51%) identified. In 26 patients, monoviral infections were found, and in 17 patients, polyviral infections were identified, the most common pattern being influenza A and B virus, followed by human rhinovirus and human parainfluenza. The most common bacteria isolated were Pseudomonas aeruginosa (9/32,28%) followed by Acinetobacter baumanii and Klebsiella pneumoniae (7/32, 21%). Among the viral–bacterial coinfection, human coronavirus NL63 infection was always associated with a bacterial infection. Conclusion: This information on the various viral and bacterial etiologies of respiratory infections in AECOPD in this part of India will improve the understanding of the management of AECOPD using a timely institution of antivirals and reduce the overuse of antibiotics and the implementation of routine influenza vaccination.

Introduction: Retrospective studies have shown improved diagnostic yield of combined cytology and cell blocks specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with variable additional yields in cell blocks. In this prospective study, we assessed the diagnostic performance of cytology and cell blocks in patients undergoing EBUS-TBNA. Methods: This was a single-center, cross-sectional study conducted between December 2017 and November 2019 including patients aged ≥18 years with mediastinal lymphadenopathy. EBUS-TBNA was performed under conscious sedation using 22G needles. Both cytology smears and cell blocks by the tissue coagulum clot technique were prepared for each patient without rapid on-site evaluation. Results: Data were analyzed for 93 patients (mean age 54.25 ± 13.7 years, 73 males) where both cytology and cell blocks were available. Sample adequacy was 100%. Overall diagnostic yield either by cytology or cell block was 83%. Cytology yield was 79.6%, whereas cell block was diagnostic in 73% of patients (P < 0.001). The overall additional yield of cell blocks was 3.2%. Cell blocks had additional yields of 1.8%, 0%, and 14.3% in malignancy, tuberculosis, and sarcoidosis, respectively. Tumor histology was better identified in 76% of positive cell blocks, and accurate histological subtyping was possible in 32.6% cases. Immunohistochemistry was feasible in 82.5% of all positive cell blocks, and these were judged to be adequate for the mutational analysis. Conclusions: Compared to cytology, EBUS-TBNA cell blocks did not significantly increase the overall diagnostic yield in unselected patients. However, cell blocks are beneficial in the characterization of tumor morphology and histological subtyping of lung cancer.

BackgroundLong COVID or long-term symptoms after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe acute COVID-19 cases. We did this study to estimate the incidence and identify the characteristics and predictors of Long COVID among our patients.MethodologyWe recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks and six months of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.ResultsWe have analyzed 487 and 371 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47) and 223 days (IQR:195,251), respectively. Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) and 9.4% (95% CI: 6.7%,12.9%) of participants at four weeks and six months of follow-up, respectively. Incidence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n = 72) at four weeks of follow-up. At six months, the incidence among mild/moderate (n = 319) was 7.2% (95% CI:4.6%,10.6%) as compared to 23.1% (95% CI:12.5%,36.8%) in severe/critical (n = 52). The most common Long COVID symptom was fatigue. Statistically significant predictors of Long COVID at four weeks of follow-up were-Pre-existing medical conditions (Adjusted Odds ratio (aOR) = 2.00, 95% CI: 1.16,3.44), having a higher number of symptoms during acute phase of COVID-19 disease (aOR = 11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR = 2.32, 95% CI: 1.17,4.58), the severity of illness (aOR = 5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR) = 3.89, 95% CI: 2.49,6.08).ConclusionA considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.

BackgroundIvermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers.MethodsA hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection.ResultsIvermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection.ConclusionTwo-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic.

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is routinely performed for diagnostic evaluation of mediastinal lymphadenopathy due to various etiologies with excellent sensitivity and specificity. Melioidosis can have atypical features like isolated mediastinal lymphadenopathy mimicking as tuberculosis or lymphoma. Differentiation of such atypical melioidosis presentation become difficult due to similar clinical, radiological and even similar EBUS lymph node characteristics. Role of EBUS TBNA in diagnosing melioidosis is under investigated and sparsely reported. We describe two cases of melioidosis diagnosed by point of care rapid lateral flow immunoassay antigen testing and culture of EBUS-TBNA samples from necrotic mediastinal lymph nodes.

Reexpansion pulmonary edema (RPE) is an important cause of unilateral pulmonary edema that rarely occurs following drainage of pleural effusion or pneumothorax. Most patients develop symptoms within an hour of lung expansion. The presentation is usually rapid and dramatic and may be fatal at times. The duration of lung collapse more than 3 days, large-size pneumothorax, rapidity of lung expansion, and application of negative pleural suction are well-known risk factors for the development of RPE. We present here an elderly male with diabetes mellitus who presented with a large pneumothorax and developed RPE shortly after insertion of a chest tube.

Obstructive sleep apnea (OSA) is associated with significant cardiovascular andcerebrovascular morbidity and mortality. Usual parameters studied in sleep laboratoryare unable to measure overall impact of OSA on human life. Consequently, it isimportant to measure Quality of Life (QoL) in OSA. QoL can be measured with genericinstruments like SF-36 or OSA specific questionnaires like Calgary Sleep ApneaQuality of Life (SAQLI) questionnaire. Most of the studies suggest that there issignificant impairment of QoL in patients of OSA. But the present evidence suggeststhat impairment in QoL is not proportional to severity of OSA. There is no consensus onthe question of improvement in QoL with Continuous Positive Airway Pressure(CPAP) therapy. A recent Cochrane review concluded that CPAP improves QoL inpeople with moderate and severe OSA.Key words : Obstructive sleep apnea, Quality of Life, Continuous Positive AirwayPressure

Chilaiditi sign is the peculiar radiographic presentation of interposition of colon between diaphragm and liver. When associated with symptomatology, it is called as chilaiditi’s syndrome. Though rare, respiratory symptoms may be present. In such cases, it becomes difficult to determine if the symptomatology is due to the syndrome only, or there is some underlying lung involvement, until this is specifically considered in the differential diagnosis. We present a male patient, where thorough investigations revealed Interstitial Lung Disease (ILD), along with Chilaiditi sign on chest radiograph. Respiratory symptomatology responded partially to the management of underlying ILD. It is left for discussion, whether the Chilaiditi syndrome was also contributing to the overall clinical presentation or the respiratory complaints were solely due to ILD and Chilaiditi sign was an incidental finding.

Background: Several studies have demonstrated considerable impairment of quality of life (QOL) in obstructive sleep apnea (OSA) patients, but its relation with severity of OSA is yet unclear. Study Objectives: To investigate the effects of OSA on the QOL and its association with the disease severity. Design and Setting: Observational, prospective case-control study. Materials and Methods: QOL of 69 OSA patients and 41 healthy controls were assessed using the Calgary sleep apnea quality of life index (SAQLI) on the morning following the polysomnography (PSG) study. Statistics: All statistical analyses were performed using the SPSS 17.0 (SPSS Inc., Chicago). Differences between sleep-related symptoms and SAQLI subscales scores were assessed with the Chi-square test and the Student t-test. Due to non-normal distribution, differences between SAQLI scores of controls and OSA patients were evaluated using a non-parametric Mann-Whitney test. Spearman correlation and backward multiple regression analysis were used to analyze the association between SAQLI scores and sleep indices and anthropometric variables and PSG variables. Results: Study included 69 cases (57 male and 12 females) with a mean age, weight, height, neck circumference, and body mass index 48.45 ± 10.12 years, 83.03 ± 16.48 kg, 159.75 ± 28.29 cm, 44.01 ± 3.23 cm and 30.77 ± 6.71 kg/m 2 . Mean apnea-hypopnea index was 26.39 ± 16.62. The median score of four SAQLI domains daily function, social interaction, emotional, symptoms and total mean SAQLI score were 3.64 (3.46-3.90), 3.77 (3.51-3.88), 3.64 (3.53-3.83), 4.80 (4.68-5.11), 4.09 (3.88-4.09) ,and 1.36 (1.29-1.71), 1.38 (1.24-1.62), 1.45 (1.23-1.62), 2.00 (1.78-2.26), 1.55 (1.46-1.73) for patients and controls respectively. All the individual domain scores and the mean SAQLI scores of patients were significantly higher than the controls. Conclusion: OSA causes significant impairment of QOL, but the severity of impairment is not directly proportional to the severity of OSA.

Desmoid tumor is a rare, benign soft tissue tumor having potential for local invasion. It commonly arises in abdominal wall, presenting as a palpable mass. We describe a case of thoracic desmoid tumor in a middle aged male arising from the chest wall. Unlike the usual presentation, two separate non-palpable tumor masses protruded into left thoracic cavity mimicking lung carcinoma. The patient underwent successful complete surgical excision of the tumor. Such tumors, being rare, may pose diagnostic problems if not considered in the initial work up.