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.

Case series on Trichomonas vaginalis infections: impact of proper sample collection and diagnostic stewardship.

This paper elucidates the transformative impact of a strategic shift in diagnostic practices in the detection of Trichomonas vaginalis. It explores five cases where the implementation of a specific diagnostic protocol led to effective identification of the infection. In-depth discussions and a comprehensive literature review underline the necessity for precise diagnosis and the paramount importance of diagnostic stewardship in managing sexually transmitted infections.

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.

Hit or Miss: The Dilemma of Specimen Selection for Microbiological Diagnosis of Rhino-Orbital-Cerebral- COVID-Associated Mucormycosis (ROCM-CAM).

BACKGROUND: We diagnosed various cases of rhino-orbital-cerebral- COVID-associated Mucormycosis (ROCM-CAM) during India's second wave of COVID-19. This helped formulate novel suggestions for improving laboratory output, applicable anywhere in the world. METHODS: To diagnose ROCM-CAM by microbiological methods, we used direct microscopy and conventional culture on various clinical samples within the shortest turn-around time. DESIGN: Prospective single-center observational study. PARTICIPANTS: Patients with ROCM-CAM. RESULTS: Of 113 suspected cases of ROCM-CAM during May 2021, direct microscopy and culture could confirm the disease in 87.61% and 44.25% of patients, respectively. The highest pathogen isolation was seen from maxillary bone fragments, FESS-guided biopsy from pterygopalatine fossae, nasal turbinates and nasal mucosal biopsy. Direct microscopy could diagnose the disease in almost 40% of patients within 24 hours and 60% within two days. Conventional cultures yielded Rhizopus spp. (86%) as the commonest fungal pathogen followed by Mucor spp. (12%) within 7 days. Deep tissue biopsies are more useful for rapid diagnosis than superficial specimens. Routine fungal cultures can supplement case detection and help prognosticate survivors. CONCLUSION: The management of ROCM is a surgical emergency. The diagnosis of the condition must therefore be prompt and precise. Despite ongoing antifungal therapy, nasal mucosal tissue, FESSguided, and intra-operative tissue biopsies showed the pathogen's highest diagnostic yield. The diagnostic index improved further when multiple (4-5) high-quality specimens were collected. Nasal swabs and crusts, among the most commonly requested specimens worldwide, were found to have an overall low diagnostic potential.

Comparative evaluation of colistin susceptibility testing by Disk Diffusion and Broth Microdilution methods: An experience from a tertiary care hospital.

BACKGROUND: Recent times have seen uninhibited use of colistin due to emergence of carbapenem resistant gram-negative bacteria especially in India and the most common method still employed by most of the laboratories for in vitro testing of colistin is disk diffusion method. OBJECTIVE: The study aimed to compare two methods for colistin susceptibility testing Methods: This retrospective observational study was done on a total of 212 non-duplicate carbapenem resistant gram-negative isolates from patients attending our tertiary care hospital from April 2019 to June 2020. Colistin susceptibility testing for these isolates was done by disk diffusion method followed by broth microdilution method. RESULTS: We found out that disk diffusion method showed relatively low sensitivity [34.5%; 95%CI: 19.94-52.65] but high specificity [99.45%; 95% CI: 96.97 - 99.90] in detecting colistin resistant organisms in comparison to broth microdilution method. CONCLUSION: Disk diffusion method is an unreliable method at detecting colistin resistance. Therefore, we should always rely on susceptibility testing by standard broth microdilution or newly introduced broth disk elution method before dispatching the report even in resource limited settings. The early and accurate reporting of susceptibility results can preserve the therapeutic value of the drug until we have newer treatment options available in the country.

Effectiveness of BBV152/Covaxin and AZD1222/Covishield vaccines against severe COVID-19 and B.1.617.2/Delta variant in India, 2021: a multi-centric hospital-based case-control study.

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.

Surgical & medical management of ROCM (Rhino-orbito-cerebral mucormycosis) epidemic in COVID-19 era and its outcomes - a tertiary care center experience.

OBJECTIVE: To evaluate the outcome of patients with ROCM (Rhino-orbito-cerebral mucormycosis) following their medical and surgical management. MATERIALS AND METHODS: It is a prognostic study based in a tertiary care center in North-Western India. Patients who developed ROCM post COVID-19 infection from 1st September 2020 to 30th June 2021 were included in this study. Surgical debridement and administration of antifungal therapy was done for the post-COVID-19 ROCM patients. Disease progression and survival was studied up to 5 months of follow-up in the second wave. RESULTS: A total of 145 ROCM patients were included. The mean age at presentation, male: female ratio was 48.2 years and 2:1 respectively. As per our proposed new staging system and treatment strategy, the majority of patients belonged to stage II (31.72%) and stage III (31.03%). On a follow-up period of 5 months, 26 (18%) patients have lost their life and rest of the patients are on strict follow-up. CONCLUSION: ROCM is an extremely aggressive fungal infection which rapidly became an epidemic following the COVID-19 pandemic. The diverse and unique presentation led us to evolve a new strategy to classify and manage these patients.

Rapid Response Preparedness for Management of Post-Covid Invasive Rhino-Orbito-Cerebral Fungal Infections: Experience from a Tertiary Care Government Institute in India.

Sudden surge of Post Covid-19 Rhino-orbito-mucormycosis cases has left entire ENT fraternity in the center of a war room. We present a quick administrative preparedness for this situation in a tertiary care Government Institute in India. This model may serve as a reference for other centers.

Clinical Features, Radiological Findings, and Treatment Outcomes in Patients with Pulmonary Nocardiosis: A Retrospective Analysis.

Introduction Lack of specific clinical features makes the diagnosis of pulmonary nocardiosis difficult. A high index of suspicion is required for diagnosis especially in cohorts with pre-existing risk factors. This study aimed to study the clinical and radiological characteristics and outcomes in patients with pulmonary nocardiosis. Methods This was a retrospective observational study. Data of confirmed cases with pulmonary nocardiosis were collected from a digital patient management system. Results A total of eight cases of pulmonary nocardiosis were included. The mean age of patients was 50 ± 14.3 years with a female preponderance (62.5%). The most common co-morbidity was chronic lung disease (37.5%). The common clinical feature of pulmonary nocardiosis was cough with expectoration (50%) and the mean duration of symptoms was 18 days. The common radiological (CT thorax) findings were consolidation, bronchiectasis, mediastinal lymphadenopathy, and nodularity (50% each). One patient had an extension of pulmonary disease in the chest wall. Microbiological detection of Nocardia spp. was done in sputum samples (50%) and in bronchoalveolar lavage (BAL) samples (50%). Culture was positive in two BAL samples. Intravenous empirical antibiotics in combination with oral trimethoprim-sulfamethoxazole double standard (15 mg/kg trimethoprim) were started at the time of diagnosis. Ceftriaxone and amikacin were commonly used antimicrobials. Conclusion Nocardia spp. commonly causes disease in patients with pre-existing chronic disease. A high index of suspicion is required in patients with subacute to chronic respiratory symptoms, raised inflammatory markers, and the absence of common respiratory pathogens in evaluation.

Evaluation of the performance of a novel sputum processing ReaSLR methodology for culture of sputum samples in solid and liquid media in comparison with modified Petroff's method.

BACKGROUND: Early case detection by sputum smear microscopy is a crucial step in the control of pulmonary tuberculosis in high burden countries. Due to low sensitivity of this rapid and cost effective method, culture of Mycobacterium tuberculosis (MTB) is considered as the gold standard. Modified Petroff's method using 2%-4% sodium hydroxide (NaOH) and N-acetyl- l-cysteine (NALC) to digest and at the same time to decontaminate the specimen is widely used in developing countries prior to culture. This method is considered tedious and cumbersome. A novel ReaSLR (ReaMetrix's Sputum Liquefying Reagent) methodology has been proposed as a simple and low-cost method for sputum processing. This study was undertaken to evaluate the performance of the ReaSLR method of sputum processing prior to culture in comparison to the modified Petroff's method. METHODS: Early morning sputum samples, collected from suspected TB patients, were divided into two equal halves and processed by two different methods i.e modified Petroff's method and ReaSLR method. After processing with different methods, each sample was inoculated in Lowenstein Jensen (LJ) medium and Mycobacteria growth indicator tube (MGIT). Smears were also prepared from the samples processed with modified Petroff's method and graded according to Centers for Disease Control and Prevention (CDC) grading after microscopic examination. Culture results of both the methods were recorded and analysed using SPSS 20.0 version. RESULTS: On comparing different methods of sputum processing for culture in solid and liquid media, the rate of contamination in both the media was significantly high with ReaSLR method as compared with modified Petroff's method. Also, the mean time-to-detection of MTB growth in LJ medium was significantly less with modified Petroff's method i.e 30.21 days as compared to ReaSLR method (34.23 days; p < 0.001). However, the mean time-to-detection of MTB growth in MGIT was similar with both the methods. CONCLUSION: Due to the high contamination rate in solid and liquid culture media, ReaSLR method cannot be considered as an alternative to modified Petroff's method for sputum processing prior to culture. The detection of growth of MTB in LJ media was also earlier with modified Petroff's method than ReaSLR method.

Gut microbiota profiling in hematopoietic stem cell transplant recipients: Towards personalized medicine.

BACKGROUND: Antibiotic resistance in bacteria is a cause for concern, especially in hematopoietic stem cell transplant (HSCT) patients. Endogenous bowel microflora in HSCT patients get replaced by hospital multidrug resistant flora and pose risk of serious bacterial infection during the pre-engraftment stage. For decades, many methods to reduce the translocation of gut microbiota in HSCT patients have been attempted. Despite the logic, of using prophylactic antibiotics, there is no consensus on standard regimen. Personalized antibiotic prophylaxis-based on gut microbiota and clinical profile has been suggested by researchers. In this study, gut microbiota in HSCT recipients has been studied with antimicrobial susceptibility testing and detection of various antibiotic resistance phenotypes. METHODS: Seventy-six HSCT patients (2016-2018) were included. Stool surveillance cultures and antibiotic susceptibility testing were performed. Bacterial isolates were classified into various antibiotic resistance phenotypes. RESULTS: This study revealed that 73.75% HSCT recipients had gut colonized with antibiotic resistance microbiota which included extended-spectrum ß-lactamase-, multidrug- and extensively drug-resistant phenotypes. CONCLUSION: This study reiterates the importance of individual profiling of gut microbiota in HSCT patients.

New-onset hyperglycaemia and prolonged systemic corticosteroids therapy in mild COVID-19 patients as major risk factors for invasive mucormycosis: a preliminary study.

Background and Purpose: Rapid surge of invasive mucormycosis has surprised the Indian healthcare system amidst the coronavirus disease-19 (COVID-19) pandemic. Hence, there is an urgent need to find the risk factors for the sudden rise in cases of invasive mucormycosis among COVID-19 patients. This study aimed to find crucial risk factors for the sudden surge of invasive mucormycosis in India. Materials and Methods: This case-control study included 77 cases of COVID-19 associated mucormycosis (CAM) who matched the controls (45 controls) in terms of age , gender, and COVID-19 disease severity. The control group included subjects that matched controls without mucormycosis confirmed by reverse transcription-polymerase chain reaction at our tertiary care center during April-May 2021. Probable predisposing factors, such as duration of diabetes mellitus (DM), history of recent hospitalization, duration of hospital stay, mode of the received oxygen supplementation, and use of steroids, zinc, vitamin c, and any other specific drugs were collected and compared between the two groups. Moreover, the laboratory parameters, like glycated hemoglobin (HbA1c), highly sensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were analyzed to find out the significant association with CAM. Results: DM (Odds ratio=7.7, 95% CI 3.30-18.12; P=<0.0001) and high glycated hemoglobin level (HbA1c>7.5 gm %) (odds ratio=6.2, 95% CI 1.4-26.7; P=0.014) were significant risk factors for the development of invasive mucormycosis among the COVID-19 cases. A higher number of mild COVID-19 cases developed CAM, compared to the moderate to severe cases (59.7% vs 40.3%). Use of systemic corticosteroids (odd ratio=5 with 95% CI 1.5-16.9; P=0.007) was found to be a risk factor for invasive mucormycosis only in mild COVID-19 cases. Use of oxygen, zinc, and vitamin C supplementation, and proprietary medicine did not lead to a significant risk of invasive mucormycosis in cases, compared to controls. Cases with invasive mucormycosis had a higher level of inflammatory markers (hs-CRP and ESR, P=<0.001 and 0.002, respectively), compared to the controls. Conclusion: Uncontrolled and new-onset DM and the use of systemic corticosteroids in mild cases were significantly associated with a higher risk of invasive mucormycosis in COVID-19 cases. There should be a strong recommendation against the use of systemic corticosteroids in mild COVID-19 cases.

Cytopathological diagnosis of gallbladder mass and mural thickening based on imaging findings: A prospective study of 51 cases.

BACKGROUND: Image-guided fine-needle aspiration cytology (FNAC) serves as first-line diagnostic modalities for the assessment of mural thickening of the gallbladder (GB). AIM: The main objective of the present study was to correlate the diagnostic accuracy of preoperative image-guided FNAC of the thickened GB wall based on imaging findings to arrive at a final diagnosis in a tertiary care center. MATERIALS AND METHODS: Fifty-seven image-guided fine-needle aspirations (FNAs) were performed from mural thickening of the GB over a period of 4 years and the smears prepared were stained with Leishman and Papanicolaou (Pap) stain. Out of 57 cases, 51 were included in the study for which follow-up histopathology was performed. RESULT: Out of 51 aspirations, 43 (84.3%) were adequate, 5 (9.8%) were inconclusive, and 3 (5.9%) were inadequate. Among the adequate aspirations, the most common was adenocarcinoma-36 (70.5%). The correlation between confirmatory cytological diagnosis and adequacy was significantly high (P = 0.0001). The overall diagnostic accuracy for adequate aspiration was 95.3%. The common diagnostic pitfalls were necrotic areas, aspiration of reactive hepatocytes adjacent to the GB mass, and mucus islands. No procedural complication was observed in any patient. CONCLUSIONS: Image-guided FNAC can be used as a safe, rapid, and successful diagnostic procedure with high sensitivity, specifically for supporting and confirming ultrasonography(USG)/computed tomography (CT) diagnosis of GB mass or mural thickening of the wall.