Progress and challenges in achieving tuberculosis elimination in India by 2025: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) continues to pose a significant public health challenge in India, which is home to one of the highest TB burdens worldwide. This systematic review and meta-analysis will aim to synthesize the anticipated progress and potential challenges in achieving TB elimination in India by 2025. METHODS: A comprehensive search will be conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies. The eligibility criteria will encompass individuals diagnosed with TB in India, interventions targeting TB treatment, prevention, or control, and various comparator groups. Outcomes of interest will include incidence reduction, mortality rate, treatment success rate, barriers to TB care, and more. Both quantitative and qualitative data will be synthesized, and the risk of bias will be assessed using established tools. OUTCOMES: The review is expected to provide a holistic understanding of the TB landscape in India, highlighting the effective interventions and potential challenges in the journey towards TB elimination. CONCLUSIONS: While it is anticipated that significant progress will be made in the fight against TB in India, challenges are likely to persist. This review will offer a comprehensive roadmap for researchers, policymakers, and healthcare professionals, emphasizing the importance of continued efforts, innovative strategies, and a multi-pronged approach in achieving the goal of TB elimination in India by 2025.

Prevalence of isoniazid resistance in cases of rifampicin resistance detected on GeneXpert MTB/RIF assay.

Background: The fight against tuberculosis in our country has taken a new shape with the inclusion of rapid nucleic acid amplification tests like GeneXpert MTB/RIF assay which rapidly detects Mycobacterium tuberculosis and rifampicin resistance. Rifampicin resistance detected on GeneXpert has been considered as a sine qua non for the presence of isoniazid resistance and hence classified as multidrug-resistant tuberculosis (MDR-TB). However treatment of rifampicin-resistant, isoniazid-monoresistance, and MDR-TB are different. Our study was done with the aim of identification of the prevalence of isoniazid resistance on culture, in cases which had rifampicin resistance on GeneXpert. Methods: Pulmonary samples of patients of presumptive tuberculosis were subjected to GeneXpert testing and liquid MGIT (mycobacterium growth indicator tube) culture. On detection of rifampicin resistance on MTB/RIF assay, the patients were included in our study and cultures were followed-up for sensitivity to isoniazid. A total of 76 patients were included. Results: 76 patients of rifampicin resistance on GeneXpert MTB/RIF assay were followed-up for the sensitivity of isoniazid on culture media. Out of the 76 cases, 62 (81.57%) were found to have isoniazid resistance. Out of the 14 patients, the cultures showed no growth in 6, and in the rest, isoniazid was found to be sensitive. Conclusion: GeneXpert MTB/RIF assay is an excellent modality for the detection of M. tuberculosis and rifampicin resistance. The decision to exclude isoniazid from the treatment regimen in patients with rifampicin resistance should be made only after conducting further molecular/phenotypic tests.

Transforming clinical virology with AI, machine learning and deep learning: a comprehensive review and outlook.

In the rapidly evolving field of clinical virology, technological advancements have always played a pivotal role in driving transformative changes. This comprehensive review delves into the burgeoning integration of artificial intelligence (AI), machine learning, and deep learning into virological research and practice. As we elucidate, these computational tools have significantly enhanced diagnostic precision, therapeutic interventions, and epidemiological monitoring. Through in-depth analyses of notable case studies, we showcase how algorithms can optimize viral genome sequencing, accelerate drug discovery, and offer predictive insights into viral outbreaks. However, with these advancements come inherent challenges, particularly in data security, algorithmic biases, and ethical considerations. Addressing these challenges head-on, we discuss potential remedial measures and underscore the significance of interdisciplinary collaboration between virologists, data scientists, and ethicists. Conclusively, this review posits an outlook that anticipates a symbiotic relationship between AI-driven tools and virology, heralding a new era of proactive and personalized patient care.

An unusual presentation of pulmonary nodules.

A pulmonary nodule is a common radiological finding encountered in routine medical practice. It needs to be extensively evaluated as the differential diagnosis can range from sinister malignancies to fully treatable infectious causes. Here, we present a rare case of pulmonary paragonimiasis presenting as pulmonary nodule. This case report aims to sensitise the medical practitioner regarding pulmonary paragonimiasis which is completely treatable but carries a high risk of being under diagnosed.

A very rare case of lingular sequestration.

Pulmonary sequestration also called as bronchopulmonary sequestration is a rare congenital anomaly. It is defined as a mass of dysplastic lung tissue which has no connection with the main bronchopulmonary tree and is supplied by a branch of systemic artery and drainage by the separate venous system. It can be classified into intralobar and extralobar variety, with intralobar being more common. Its incidence is around 1 per 8300 to 35000, and it constitutes about 0.15-6.4% of all congenital lung anomalies. It generally involves lower lobes with the left lobe being more common than the right. It is an uncommon entity and rarely reported in literature for lingula. Its distribution is equal in gender distribution except for extralobar variety which has a male preponderance. It generally presents with recurrent pneumonia and hemoptysis. Here, we describe a very rare case of intralobar lingular sequestration in a patient who presented with recurrent chest infections and was managed with segmentectomy.

Correlation of fraction of exhaled nitric oxide with asthma control test and asthma severity in diagnosed cases of asthma.

Background: Fraction of NO in exhaled air (FENO) has emerged as a simple, non-invasive, sensitive marker of airway inflammation in asthma diagnosis and management. Correlation studies of FENO with clinical grades of asthma and symptom burden are sparse, more so in Indian population. Hence, this study was carried out in Indian subjects to evaluate FENO correlation with asthma severity. Methods: The study was performed on 52 proven cases of asthma in the age group of 17-90 years in period of December 2016 to May 2018. All the subjects had assessment in the form of Asthma Control Test (ACT)questionnaire, FENO parts per billion measurement with a portable NO analyzer (NIOX MINO Airway Inflammation Monitor; Aerocrine) and spirometry. Statistical analysis was presented in the form of percentage (%) and mean. Results: Of a total of 52 asthma cases, 27 (51.9%) were male cases while 25 (48.1%) were female cases. Study population ranged from 17 to 82 years. Subjects categorized into 03 categories of asthma severity based on their treatment step. ACT score of ranged between 11 and 25 with a mean value of 20.27 and standard deviation of 3.73. No significant correlation was found between FENO and ACT (r) = -0.177, P-value = 0.210 (>0.05). Significant correlation between FENO and different grades of asthma severity was found with p-value 0.032 (<0.05). Conclusion: Asthma severity as assessed by the step of treatment is correlated well with FENO value in an asthmatic individual to maintain the controlled asthma status. FENO and ACT were found to have no correlation.

Pattern of skin sensitivity to various aeroallergens by skin prick test in patients of allergic airway disease in South Western Maharashtra.

Background: The prevalence of allergic diseases such as asthma and allergic rhinitis is high in the general population, and aeroallergens are the most common allergens that cause airway inflammation. Skin prick testing (SPT) is a validated method to diagnose IgE-mediated allergic diseases. The knowledge of allergen sensitivity pattern in this part of India is limited. The present study was undertaken to identify common aeroallergens prevalent in this area using a standardized SPT. Methods: We did a cross-sectional hospital-based study. A total of 330 patients of proven allergic airway disease underwent SPT. We used a validated skin prick test which included 22 allergen extracts, 1 positive control, and 1 negative control. Results: A total of 327 patients were included in the study. Two hundred seventy-one (82.27%, n = 327) patients had a positive SPT to one or more aeroallergen extract. The sensitivity of Dermatophagoides pteronyssinus (49.85%) was seen in the maximum number of people followed by Dermatophagoides farinae (47.70%). Conclusions: In our study, dust mites were the most common aeroallergen seen in maximum study subjects.

Effectiveness of high flow nasal cannula oxygen therapy in patients of acute pulmonary thromboembolism with acute hypoxemic respiratory failure.

Background: Acute Pulmonary thromboembolism (PTE) is associated with acute hypoxemic respiratory failure (AHRF), which is a leading cause of death in these patients. High-Flow Nasal Cannula (HFNC) oxygen therapy is a cornerstone of the treatment of respiratory failure. The aim of the present study is to explore the efficacy of HFNC in the treatment of patients of acute PTE with acute hypoxemic respiratory failure in India. Methods: This is a retrospective study of patients admitted to a tertiary care center with acute PTE with AHRF during the period from January 2018 to January 2020. After reviewing medical files, patients of acute PTE with AHRF treated with HFNC were included in the study. We analyzed the improvement in oxygenation parameters and respiratory rate, as well as outcome in these patients. Results: During the above specified period, 12 patients suffering from PTE with AHRF were treated with HFNC. After 1 h of the initiation of HFNC along with anticoagulation, the respiratory parameters of patients significantly improved. HFNC was applied for a period of 6-10 days. None of the patients required intubation for AHRF, and all patients were discharged from the hospital on oral anticoagulants. Conclusion: HFNC oxygen therapy in patients with acute PTE with AHRF showed rapid improvement of oxygenation and respiratory rate. HFNC oxygen therapy is an efficacious treatment for patients with AHRF secondary to acute PTE without any significant hemodynamic effect. It acts as a superior modality of oxygen therapy avoiding noninvasive and invasive ventilatory support.

Phenytoin-induced organising pneumonia: An unknown entity.

Organising pneumonia can be idiopathic or as a result of other inciting factors such as drugs. Phenytoin has been implicated in significant side effects predominantly involving extrapulmonary sites. Pulmonary side effects are reported less frequently. Hereby, we report a first case of phenytoin-induced organising pneumonia from India and evidence of significant improvement after stopping the drug.

Evaluation of a novel sputum processing ReaSLR methodology for improving sensitivity of smear microscopy in clinical samples.

Background: Early case detection is a crucial step in the control of tuberculosis (TB). Sputum smear microscopy is the primary method of TB diagnosis in developing countries. The modified Petroff's method using sodium hydroxide at concentrations ranging between 2% and 4% to digest the specimen is widely used in developing countries. A novel ReaSLR (ReaMetrix's Sputum Liquefying Reagent) methodology has been proposed as a simple, easy, low-cost, and better alternative to conventional methods for sputum processing. This study was undertaken to evaluate the performance of the ReaSLR method of sputum processing in comparison with that of the modified Petroff's method. Methods: Early-morning sputum samples were collected. After preparing a direct smear, each sample was divided into two equal halves and processed by both the methods, i.e., modified Petroff's method and ReaSLR method. Direct smears were graded according to Revised National Tuberculosis Control Program grading, and smears prepared after processing by the two different methods were graded according to Center for Disease Control and Prevention grading. Smear microscopy results were compared taking culture results of samples processed by the modified Petroff's method as the gold standard. Results: The rate of smear positivity with the modified Petroff's method (22.22%) was found to be higher than that with direct smear microscopy (13.56%; p = 0.0002) and the ReaSLR method (17.32%; p = 0.04). The modified Petroff's method was found to be 26.76% more sensitive than direct microscopy and 15.59% more sensitive than the ReaSLR method. Conclusion: The ReaSLR method was not superior to the modified Petroff's method for smear microscopy. Although this method was more sensitive than the direct method in smear microscopy, the modified Petroff's method performed much better than the ReaSLR method.

Utility of P-SEP, sTREM-1 and suPAR as Novel Sepsis Biomarkers in SARS-CoV-2 Infection.

The coronavirus disease 2019 is a highly contagious viral infection caused by SARS-CoV-2 virus, member of coronaviridae family. It causes life threatening complications due to complexity and rapid onset course of the disease. Early identification of high-risk patients who require close monitoring and aggressive treatment remains challengeable till date. Novel biomarkers which help to identify high risk patients at the early stage is high priority. Objective of this review to find utility of P-SEP, sTREM-1 and suPAR for diagnosis, risk stratification and prognosis of SARS-CoV-2 infected cases. Soluble receptors like, P-SEP, sTREM-1 and suPAR have been involved in immune regulation in SARS-CoV-2 infection and elevate more in severe cases. A comprehensive research of databases like PubMed, EMBASE, CNKI and Web of Science was performed for relevant studies. A total of nine out of fifteen research literature in initial screening were included for this review. Interestingly all studies have reported high levels of P-SEP, sTREM-1 and suPAR in SARS-CoV-2 infected cases and the biomarkers positively correlated with severity of infection. This implies that P-SEP, sTREM-1 and suPAR can be implemented as surrogate marker in blood profile for early diagnosis, risk stratification and prognosis in SARS-CoV-2 for better management in Indian population at the current situation.

Functional impairment in bronchiectasis: Spirometry parameters versus St. George's Respiratory Questionnaire scores: Any co-relation?

OBJECTIVES: Bronchiectasis is a common respiratory disease which has significant morbidity and mortality. Health-related quality of life scores are not routinely used for the assessment of bronchiectasis. The present study was undertaken with an aim to assess the clinical profile and functional impairment using spirometry in patients with bronchiectasis and to co-relate functional impairment with their St. George's Respiratory Questionnaire (SGRQ) score. METHODOLOGY: This was a cross-sectional study carried out on 102 patients of bronchiectasis. All patients were assessed for clinical profile, spirometry, and SGRQ scores. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were measured and compared with SGRQ scores. Data analysis was done using SPSS version 20.0 and MS-Excel. RESULTS: Obstruction was found in 62.7% and significant bronchodilator reversibility was observed in 30.4%. All spirometry parameters individually and combined showed a negative co-relation which was stastically significant (P < 0.001). Best co-relation was with FEV1 r = -0.809; symptom score, r = -0.821; activity score, r= -0.849; impact score and r = -0.873 total score. FVC% versus symptoms score r = -0.735; activity score r = -0.729, impacts score r = -0.778; total score r = -0.792. FEV1/FVC versus symptoms score r = -0.227, activity score r = -0.278, impacts score r = -0.263, total score r = -0.274. CONCLUSION: SGRQ scores have shown good correlation with functional impairment. It can be used as a modality to evaluate health status of patient in resource constraint settings.

Management of primary pulmonary alveolar proteinosis: A multicentric experience.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of surfactant material with reduced lung function and resulting hypoxemia. It is characterized by a variable clinical course, and whole lung lavage (WLL) is the standard treatment. Herein, we report our multicentric experience of management of primary PAP. MATERIALS AND METHODS: This retrospective study included patients with PAP managed at various armed forces respiratory centers from 2009 to 2019. The diagnosis of primary PAP was based on histopathologic confirmation on transbronchial lung biopsy or open lung biopsy and absence of causes of secondary PAP. We analyzed the response to WLL in these patients as well as the safety of the procedure. RESULTS: During the above-specified period, ten patients with a diagnosis of PAP were admitted to various armed forces respiratory centers. The median age of the patients was 34.5 years (range 23-59); there were nine males (90%). The mean duration (± standard deviation) of symptoms was 10.8 (±2.70) months. For management, WLL was done for eight patients with a median volume of 23.5 L (range 18-45) per patient. All the patients showed significant symptomatic response as well as improvement in physiological parameters with no major complications. The median follow-up of all patients was 18 (range 5-44) months. CONCLUSIONS: WLL is a safe, effective therapy in an experienced setting in patients with PAP and provides long-lasting benefits.

Bronchoscopic lung cryobiopsy for the diagnosis of pulmonary alveolar proteinosis in a hypoxemic patient.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the intra-alveolar accumulation of surfactant due to macrophage dysfunction or the production of abnormal surfactant. Diagnosis is usually confirmed by lung biopsy either bronchoscopically or by video-assisted thoracoscopic surgery. Bronchoscopic lung cryobiopsy (BLC) is increasingly being utilized for the histopathological diagnosis of diffuse parenchymal lung diseases; however, it has rarely been reported for PAP. We report a case of 59-year-old male who presented to our center with gradually worsening breathlessness and cough of 1-year duration. Chest radiograph revealed bilateral extensive pulmonary infiltrates and high-resolution computerized tomography scan revealed extensive bilateral ground-glass opacities with areas of sparing. BAL and transbronchial lung biopsy failed to confirm the diagnosis; hence, BLC was done which revealed pathologic findings suggesting PAP. BLC appears to be a promising diagnostic tool for the diagnosis of PAP and offers several diagnostic advantages compared to conventional techniques.

Exhaled nitric oxide as a guiding tool for bronchial asthma: A randomised controlled trial.

BACKGROUND: Evidence regarding the role of non-invasive marker of airway inflammation, fractional exhaled nitric oxide (FeNO) to guide asthma treatment is equivocal. We aimed to evaluate if the use of FeNO to adjust inhaled corticosteroid treatment resulted in reduced daily corticosteroid use and lesser exacerbations. METHODS: 100 patients of bronchial asthma in the age group of 12-70 years were randomised to receive inhaled corticosteroids based on either FeNO measurements (n = 50) or as per Global Initiative for Asthma (GINA) guidelines. Follow up was done every 2 months for period of 12 months. Results were compared in terms of mean daily inhaled corticosteroid use and number of exacerbations. RESULTS: After the follow up period of 12 months, mean daily dose of ICS (SD) required in FeNO group was 267.5 µg (126.29), as opposed to control group in which mean daily dose of steroid was 320.00 µg (138.69). However this observed difference in steroid dose was statistically insignificant (p value = 0.061). The estimated mean (SD) rate of asthma exacerbation experienced in follow up period of 12 months in FeNO group was 0.3 episodes (0.54) per patient per year (95% confidence interval, 0.145-455) and 0.4 episodes (0.61) per patient per year in control group (95% confidence interval, 0.228-572). However this difference in rate of exacerbations between the two study groups was not statistically significant (p = 0.387). CONCLUSION: FeNO guided management strategy for asthma did not result in statistically significant reduction in dose of inhaled corticosteroids or number of asthma exacerbations.

Bronchoscopic device closure of postoperative bronchopleural fistulae: Novel devices and innovative techniques.

BACKGROUND: Bronchoscopic device closure plays a significant role in the nonsurgical management of bronchopleural fistulae (BPF). Herein, we describe our 10-year experience in the management of postoperative BPF using various device closure modalities. This is the largest series of bronchoscopic device closure of BPF being reported from India. MATERIALS AND METHODS: This was a retrospective analysis of data of patients who underwent bronchoscopic device closure with various techniques for the management of postoperative BPF. In total, 11 patients (six males and five females) with a mean age (±standard deviation) of 42.72 ± 14.40 years with BPFs were treated with various bronchoscopic interventions for BPF closure. We used various devices such as endobronchial coils, occluder devices, and covered tracheobronchial self-expandable stents for BPF closure depending on the size of air leaks. We describe the various devices used, technique, and outcome of bronchoscopic management of BPF. RESULTS: All our patients had developed BPFs postoperatively. Pulmonary tuberculosis was the most common etiology seen in nine of our patients. All the devices were placed using a fiberoptic bronchoscope, and all patients were followed up for a minimum duration of 6 months. We successfully localized and closed BPFs in nine (81.81%) of our patients. CONCLUSIONS: Bronchoscopic device closure can be a successful strategy to manage postoperative BPF with minimal complications.

Evaluation of Microscopic observation drug susceptibility (MODS) assay as a rapid, sensitive and inexpensive test for detection of tuberculosis and multidrug resistant tuberculosis.

BACKGROUND: Microscopic observation drug susceptibility (MODS) assay has been suggested as a low cost method for rapid, accurate detection of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB). METHODS: A total of 2424 samples collected from 1063 eligible patients of suspected pulmonary or extrapulmonary TB were subjected to MODS assay. Performance of MODS was compared with culture and drug susceptibility testing (DST) by conventional solid Lowenstein-Jensen (LJ) media or liquid Mycobacteria Growth Indicator Tube (MGIT) culture. RESULTS: When compared to reference gold standard of positivity in either solid or liquid reference culture, the MODS assay had sensitivity, specificity, positive predictive value and negative predictive value of 91.3%, 98.2%, 96.0% and 95.9% respectively. MODS took a median time of 10.3 days to culture positivity as compared to 13.8 days using MGIT and 30.5 days using LJ culture. Culture and DST being concurrent in MODS, the median turnaround time for DST was the same as that for culture i.e. 10.3 days. The overall median turn around time for culture positivity and DST using manual MGIT and LJ medium was 23.6 days and 61.2 days respectively. The concordance between MODS culture and the reference susceptibility method was 97.7% for rifampicin, 95.6% for isoniazid, 98.5% for rifampicin and isoniazid. The cost of performing a single MODS assay was INR 200. CONCLUSION: MODS is a rapid and sensitive, yet simple and inexpensive test that may be helpful to enhance diagnostic accuracy, and case detection of TB and MDR-TB in resource constrained settings.

Bronchial artery embolization in treatment of hemoptysis: Treatment efficacy and complications at a tertiary care chest centre.

BACKGROUND: Hemoptysis is one of the most alarming condition to both the patients suffering from it and the treating physicians. It is caused due to varied etiologies. One of the emergent and at times life-saving treatment option is by minimally invasive interventional radiological technique of Bronchial Atery Embolization (BAE). The authors aimed to carry out a retrospective analysis of short term efficacy and safety of all patients treated by this technique at a tertiary care thoracic centre. METHODS: A total of 52 patients were included in the study who had a median follow up of 35 days. All these patients were referred for hemoptysis, intractable hemoptysis not controlled by conservative management or massive hemoptysis. An analysis of the underlying etiology, immediate and short term outcomes and complications was made. RESULTS: The study showed Tuberculosis and its sequel (bronchiectasis and chronic fibrotic changes) as the commonest etiology (65%). The BAE showed high short term efficacy (92%) in stopping the hemoptysis with a relatively low complication rate especially of major complications such as spinal cord ischemia (1.9%). The study strengthens the limited Indian data available on the subject and based on its outcome, BAE should be tried in all patients presenting with uncontrollable or massive hemoptysis not getting relief by conservative management alone. CONCLUSION: BAE is a very effective procedure with very less complications for management of massive or uncontrollable hemoptysis.

A Five-Year Study of Intrapleural Fibrinolytic Therapy in Loculated Pleural Collections.

BACKGROUND: Pleural fluid loculations due to complicated parapneumonic effusion (CPE), empyema, tubercular effusion and traumatic hemothorax can be managed either by video-assisted thoracoscopic surgery (VATS) or intrapleural ibrinolytic therapy (IPFT). The former is more invasive, not easily available and is also more expensive. On the other hand, IPFT is less invasive, cheaper, easily accessible and if used early, in loculated pleural collections, break loculations and early pleural peel, thereby facilitating pleural space drainage. OBJECTIVE: To study the efficacy of IPFT in facilitating pleural space drainage in loculated pleural collections of diverse aetiologies. METHODS: A five-year retrospective, observational study of 200 patients, with loculated pleural collections and failed tube drainage and managed with IPFT was carried out. Responders were defined as those with significant volume of fluid drained and significant radiological resolution. RESULTS: There were 106 (53%) cases of CPE, 59 (29.5%) cases of tubercular effusion, 23 (11.5%) cases of empyema and 12 (6%) cases of hemothorax. Responders were 148 (74%) in number. The distribution of responders as per type of loculated pleural collection was as follows: CPE 88 (83%), tubercular 37 (62.7%), empyema 14 (60.8%) and traumatic hemothorax 11 (91.6%). The adverse effects were mild and included chest pain in six patients and low-grade transient fewer in three cases. CONCLUSIONS: Intrapleural fibrinolytic therapy is a safe and cost-effective option in the management of selected patients with loculated pleural effusions.