NobleBlocks

Central Leprosy Teaching & Research Institute

governmentChengalpattu, Tamil Nadu, India

Research output, citation impact, and the most-cited recent papers from Central Leprosy Teaching & Research Institute (India). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
574
Citations
7.2K
h-index
40
i10-index
199
Also known as
Central Leprosy Teaching & Research InstituteLady Willigdon leprosy sanatorium

Top-cited papers from Central Leprosy Teaching & Research Institute

Constructing care cascades for active tuberculosis: A strategy for program monitoring and identifying gaps in quality of care
Ramnath Subbaraman, Ruvandhi R. Nathavitharana, Kenneth H. Mayer, Srinath Satyanarayana +3 more
2019· PLoS Medicine219doi:10.1371/journal.pmed.1002754

The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome. This approach was first used to evaluate HIV care and has since been applied to other diseases. The tuberculosis (TB) community has only recently started using care cascade analyses to quantify gaps in quality of care. In this article, we describe methods for estimating gaps (patient losses) and steps (patients retained) in the care cascade for active TB disease. We highlight approaches for overcoming challenges in constructing the TB care cascade, which include difficulties in estimating the population-level burden of disease and the diagnostic gap due to the limited sensitivity of TB diagnostic tests. We also describe potential uses of this model for evaluating the impact of interventions to improve case finding, diagnosis, linkage to care, retention in care, and post-treatment monitoring of TB patients.

Carbapenemase-producing Enterobacteriaceae: Risk factors for infection and impact of resistance on outcomes
Shanthi Mariappan, Uma Sekar, Arunagiri Kamalanathan
2017· International Journal of Applied and Basic Medical Research107doi:10.4103/2229-516x.198520

Background: Carbapenemase-producing Enterobacteriaceae (CPE) have increased in recent years leading to limitations of treatment options. The present study was undertaken to detect CPE, risk factors for acquiring them and their impact on clinical outcomes. Methods: This retrospective observational study included 111 clinically significant Enterobacteriaceae resistant to cephalosporins subclass III and exhibiting a positive modified Hodge test. Screening for carbapenemase production was done by phenotypic methods, and polymerase chain reaction was performed to detect genes encoding them. Retrospectively, the medical records of the patients were perused to assess risk factors for infections with CPE and their impact. The data collected were duration of hospital stay, Intensive Care Unit (ICU) stay, use of invasive devices, mechanical ventilation, the presence of comorbidities, and antimicrobial therapy. The outcome was followed up. Univariate and multivariate analysis of the data were performed using SPSS software. Results: Carbapenemase-encoding genes were detected in 67 isolates. The genes detected were New Delhi metallo-β-lactamase, Verona integron-encoded metallo-β-lactamase, and oxacillinase-181.Although univariate analysis identified risk factors associated with acquiring CPE infections as ICU stay (P = 0.021), mechanical ventilation (P = 0.013), indwelling device (P = 0.011), diabetes mellitus (P = 0.036), usage of multiple antimicrobial agents (P = 0.007), administration of carbapenems (P = 0.042), presence of focal infection or sepsis (P = 0.013), and surgical interventions (P = 0.016), multivariate analysis revealed that all these factors were insignificant. Mortality rate was 56.7% in patients with CPE infections. By both univariate and multivariate analysis of impact of the variables on mortality in these patients, the significant factors were mechanical ventilation (odds ratio [OR]: 0.141, 95% confidence interval [CI]: 0.024–0.812) and presence of indwelling invasive device (OR: 8.034; 95% CI: 2.060–31.335). Conclusion: In this study, no specific factor was identified as an independent risk for acquisition of CPE infection. However, as it is evident by multivariate analysis, there is an increased risk of mortality in patients with CPE infections when they are ventilated and are supported by indwelling devices.

blaIMP and blaVIM mediated carbapenem resistance in Pseudomonas and Acinetobacter species in India
M Shanthi Amudhan, Uma Sekar, Arunagiri Kamalanathan, B Sekar
2012· The Journal of Infection in Developing Countries98doi:10.3855/jidc.2268

INTRODUCTION: The emergence and rapid spread of blaIMP and blaVIM metallo-beta-lactamase (MBL) producing Gram-negative bacteria causing nosocomial infections are of concern worldwide due to limited treatment options. METHODOLOGY: A total of 179 nonreplicate, consecutive, carbapenem resistant Pseudomonas aeruginosa (61), Acinetobacter baumannii (116), Acinetobacter lwoffii (1) and Pseudomonas stutzeri (1) isolated from patients hospitalized for 48 hours or more were included in the study. The minimum inhibitory concentrations (MIC) to imipenem and meropenem were determined and interpreted according to Clinical Laboratory Standards Institute guidelines. The Modified Hodge Test (MHT) and inhibitor potentiated disk diffusion tests with ethylenediaminetetraacetic acid (EDTA) were used for screening of carbapenamases and MBL production respectively. Polymerase chain reaction (PCR) was performed for the detection of MBL (blaVIM and blaIMP) genes. Gene sequencing was performed for representative isolates. RESULTS: MHT was positive in 94.4% (n = 169). MBL screening with EDTA was positive in 80.4% (n = 144). MBL genes bla VIM and bla IMP were detected in 92 (51.4%) isolates. Bla VIM alone was detected in 89 isolates while two isolates had bla IMP alone. One isolate had both bla VIM and bla IMP. Among the P. aeruginosa, 36 carried the MBL gene. In A. baumannii, 54 carried the MBL gene. Bla VIM was found in P. stutzeri and A. lwoffii isolates. CONCLUSION: Carbapenem resistance in P. aeruginosa and A. baumannii is chiefly mediated by MBL production. The common MBL gene is the blaVIM.

OXA beta-lactamase-mediated carbapenem resistance in Acinetobacter baumannii
SM Amudhan, Uma Sekar, Kavita Arunagiri, B Sekar
2011· Indian Journal of Medical Microbiology76doi:10.4103/0255-0857.83911

OBJECTIVES: Acinetobacter baumannii is a significant pathogen in health care settings. In recent years, an increase in carbapenem resistance among A. baumannii due to Ambler class B metallo-beta-lactamases or class D OXA carbapenamases has been reported. In this study we detected the presence of OXA carbapenamases and coproduction of metallo-beta-lactamases (blaVIM and blaIMP ) by phenotypic and genotypic methods in carbapenem resistant clinical isolates of Acinetobacter baumannii. MATERIALS AND METHODS: A total of 116 consecutive, non-duplicate carbapenem resistant A. baumannii isolated from various clinical specimens were included in the study. The modified Hodge test and inhibitor potentiated disk diffusion tests were done for the screening of carbapenamase and metallo-beta-lactamase production, respectively. Polymerase chain reaction (PCR) was performed for the detection of OXA (blaOXA 23 like, blaOXA 24 like, blaOXA-51 like and blaOXA-58 like genes) and metallo-beta-lactamases (blaVIM and blaIMP ) genes. Gene sequencing was performed for representative isolates. RESULTS: Among 116 A. baumannii, OXA genes were detected in 106 isolates. BlaOXA 51 like (n = 99) and blaOXA -23 like (n = 95) were the most common and they coexisted in 89 isolates. blaOXA-24 like gene was detected in two isolates of which one also carried blaOXA-51 like and blaOXA-58 like genes. The modified Hodge test was positive in 113 isolates. The metallo-beta-lactamase screening test was positive in 92 isolates. blavim was detected in 54 isolates of which 1 also carried the blaIMP gene. CONCLUSIONS: blaOXA-23 like and bla OXA 51 like genes are the most common types of OXA carbapenamases while the blaVIM type is the most common type of metallo-beta-lactamase contributing to carbapenem resistance in clinical isolates of A. baumannii. The coproduction of OXA and metallo-beta-lactamases is not an uncommon phenomenon in A. baumannii.

TWO-TAILED TRANSFER OF TIBIALIS POSTERIOR FOR CORRECTION OF DROP-FOOT IN LEPROSY
H Srinivasan, S. M. Mukherjee, R. A. Subramaniam
1968· Journal of Bone and Joint Surgery - British Volume66doi:10.1302/0301-620x.50b3.623

1. The results of thirty-nine operations for correction of drop-foot in thirty-three patients with leprosy are discussed. 2. The procedure used was circumtibial, subcutaneous, two-tailed, tendon-to-tendon transfer of the tibialis posterior to extensor hallucis longus and to extensor digitorum longus and peroneus tertius. The motor slips were inserted into the recipient tendons on the dorsum of the foot. 3. Analysis of the results showed some correlation between the angle of active dorsiflexion and the range ofactive movement ofthe ankle. The angle ofdorsiflexion seemed to determine the range of movement. 4. When contracture of the tendo calcaneus was present, simultaneous lengthening improved the angle of dorsiflexion more than the range of active movement. 5. The causes of failure were sepsis, failure of re-education and unrecognised tightness of the tendo calcaneus. 6. The advantages of the present procedure are mentioned.

Autophagy Is an Innate Mechanism Associated with Leprosy Polarization
Bruno Jorge de Andrade Silva, Mayara Garcia de Mattos Barbosa, Priscila R. Andrade, Helen Ferreira +4 more
2017· PLoS Pathogens63doi:10.1371/journal.ppat.1006103

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages.

99DOTS
Andrew Cross, Nakull Gupta, Brandon Liu, Vineet Nair +4 more
201960doi:10.1145/3287098.3287102

Ensuring that patients adhere to prescribed medication remains an important challenge in global health. While technology has been utilized to monitor and improve adherence, solutions to date have been too costly for large-scale deployment in developing regions. This paper describes 99DOTS, a low-cost approach for tracking adherence using a combination of paper packaging and low-end mobile phones. Every day, patients reveal an unpredictable phone number behind the pills and send a free call to that number to indicate that drugs were dispensed and taken. Within five years of its inception, 99DOTS has become a standard of care for tuberculosis in India and has enrolled over 200,000 patients. We provide a holistic account of the project's evolution, including its iterative design, scaled implementation, and lessons learned along the way. We hope this account will serve as a useful case study for anyone seeking to establish and scale new low-cost technologies for a global audience.

WHO Ten threats to global health in 2019: Antimicrobial resistance.
Pugazhenthan Thangaraju, Sajıtha Venkatesan
2019· Çukurova medical journal (Online)/Çukurova medical journal57doi:10.17826/cumj.514157

-

The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression
J. Sales, Flávio Alves Lara, Thaís Porto Amadeu, Tatiana de Oliveira Fulco +4 more
2011· Clinical & Experimental Immunology50doi:10.1111/j.1365-2249.2011.04412.x

To elucidate further the possible role of the tryptophan, rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) in leprosy, the distribution of IDO-positive cells and IDO activity in the skin biopsies and sera of these patients representing the entire spectrum of the disease were studied. An increased number of macrophages/dendritic cells (DC-lineage IDO(+) cells were found in lepromatous (LL) compared to tuberculoid (BT) and reversal reaction (RR) patients. IDO-positive cells showing CD68 and CD86 surface markers predominated in LL lesions, while higher levels of IDO activity were observed in the sera of LL versus BT patients. Tests revealed an increased IDO message in Mycobacterium leprae-stimulated peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) and increased IDO expression in M. leprae-stimulated CD14(+) cells of both healthy controls (HC) and LL patients, as evaluated via flow cytometry. Increased M. leprae-induced IDO-protein synthesis was also confirmed by Western blot. Based on our in vitro studies, it was confirmed that M. leprae up-regulated IDO expression and activity in HC and LL monocytes. Interferon (IFN)-γ synergized with M. leprae in promoting IDO expression and activity in monocytes. IDO expression induced by both IFN-γ and M. leprae was abrogated by 1-methyltryptophan (1-MT). Our data suggest that M. leprae chronic infection activates the suppressive molecule IDO which, in turn, contributes to the specific immunosuppression observed in LL leprosy.

Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
Reji Manjunathan, Vijayalakshmi Periyaswami, Kartik Mitra, A. Sherlin Rosita +4 more
2022· BMC Bioinformatics49doi:10.1186/s12859-022-04724-9

BACKGROUND: The Transmembrane Serine Protease 2 (TMPRSS2) of human cell plays a significant role in proteolytic cleavage of SARS-Cov-2 coronavirus spike protein and subsequent priming to the receptor ACE2. Approaching TMPRSS2 as a therapeutic target for the inhibition of SARS-Cov-2 infection is highly promising. Hence, in the present study, we docked the binding efficacy of ten naturally available phyto compounds with known anti-viral potential with TMPRSS2. The aim is to identify the best phyto compound with a high functional affinity towards the active site of the TMPRSS2 with the aid of two different docking software. Molecular Dynamic Simulations were performed to analyse the conformational space of the binding pocket of the target protein with selected molecules. RESULTS: Docking analysis using PyRx version 0.8 along with AutoDockVina reveals that among the screened phyto compounds, Genistein shows the maximum binding affinity towards the hydrophobic substrate-binding site of TMPRSS2 with three hydrogen bonds interaction ( - 7.5 kcal/mol). On the other hand, molecular docking analysis using Schrodinger identified Quercetin as the most potent phyto compound with a maximum binding affinity towards the hydrophilic catalytic site of TMPRSS2 ( - 7.847 kcal/mol) with three hydrogen bonds interaction. The molecular dynamics simulation reveals that the Quercetin-TMPRSS complex is stable until 50 ns and forms stable interaction with the protein ( - 22.37 kcal/mol of MM-PBSA binding free energy). Genistein creates a weak interaction with the loop residues and hence has an unstable binding and exits from the binding pocket. CONCLUSION: The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin and Genistein or developing a novel drug in the combination of Quercetin and Genistein could be the brilliant choices to prevent SARS-Cov-2 infection when we consider the present chaos associated with vaccines and anti-viral medicines.

Predictors of mortality among hospitalized COVID-19 patients and risk score formulation for prioritizing tertiary care—An experience from South India
Gopalan Narendran, Sumathi Senthil, N Prabakar, Thirumaran Senguttuvan +4 more
2022· PLoS ONE47doi:10.1371/journal.pone.0263471

BACKGROUND: We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission. METHODS AND FINDINGS: Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among 'survivors' and 'non-survivors'. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 "survivors" and 259 "non-survivors" (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40-70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO2<95%; 2.96 (1.71-5.18), Urea ≥50 mg/dl: 4.51 (2.59-7.97), Neutrophil-lymphocytic ratio (NLR) >3; 3.01 (1.61-5.83), Age ≥50 years;2.52 (1.45-4.43), Pulse Rate ≥100/min: 2.02 (1.19-3.47) and coexisting Diabetes Mellitus; 1.73 (1.02-2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO2<95-11, Urea ≥50 mg/dl-15, NLR >3-11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as 'OUR-ARDs score' showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85. CONCLUSIONS: The 'OUR ARDs' risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system.

Continued proteomic analysis of <b><i>Mycobacterium leprae</i></b> subcellular fractions
Maria Angela M. Marques, Benjamin J. Espinosa, Erika K. Xavier da Silveira, María Cristina Vidal Pessolani +4 more
2004· PROTEOMICS47doi:10.1002/pmic.200400945

Recently the sequence of the Mycobacterium leprae chromosome, the only known obligate intracellular mycobacterium, was completed. It has a dramatic reduction in functional genes, with a coding capacity of only 49.5%, the lowest one so far observed among bacterial genomes. The leprosy bacillus seems to preserve a minimal set of genes that allows its survival in the host. The identification of genes that are actually expressed by the bacterium is of high significance in the context of mycobacterial pathogenesis. In this current study, a proteomic approach was undertaken to identify the proteins present in the soluble/cytosol and membrane subcellular fractions obtained from armadillo derived M. leprae. Proteins from each fraction were separated by two-dimensional gel electrophoresis (2-DE) and identified by mass spectrometry. A total of 147 protein spots were identified from 2-DE patterns and shown to comprise products of 44 different genes, twenty eight of them corresponding to new proteins. Additionally, two highly basic proteins (with pI >10.0) were isolated by heparin affinity chromatography and identified by N-terminal sequencing. This study constitutes the first application of proteomics to a host-derived Mycobacterium.

Canagliflozin: A novel SGLT2 inhibitor for type 2 diabetes mellitus
Harmanjit Singh, Pugazhenthan Thangaraju, Jasbir Singh, Shaveta Kaushal
2014· North American Journal of Medical Sciences45doi:10.4103/1947-2714.128471

Diabetes Mellitus continues to be a major non- communicable disease with global burden of 366 million at present and projected to increase to 439 to 552 million by 2030, India being the hub of diabetes. Sodium glucose transporter 2 (SGLT2) inhibitors presents a new class of anti-diabetic drugs having an insulin-independent mechanism that offers a considerable advantage of increasing urinary glucose excretion without inducing hypoglycemia and promoting weight loss due to loss of 300 to 400kcal/day, Canagliflozin being the 1(st) successful candidate of this group and became the first SGLT2 inhibitor to be FDA approved on March 29, 2013. In various clinical trials, it has shown promising results in controlling glycemia, causing weight loss, reducing systolic and diastolic BP and cardiovascular risk. There are some safety concerns associated with its use e.g. genital mycotic infections, increased urination, urinary tract infection and hyperkalemia, which need to be carefully addressed while using this drug.

Detection of New Delhi metallo beta lactamase-1 (NDM-1) carbapenemase in Pseudomonas aeruginosa in a single centre in southern India.
Shanthi Mariappan, Uma Sekar, Arunagiri Kamalanathan, B Sekar
2014· PubMed41

BACKGROUND & OBJECTIVES: New Delhi metallo β-lactamase-1 (NDM-1) producing Pseudomonas aeruginosa isolates are potential threat to human health. This study was conducted to detect the presence of bla(NDM-1) in carbapenem resistant P. aeruginosa in a tertiary care center in southern India. METHODS: Sixty one carbapenem resistant clinical isolates of a total of 212 P. aeruginosa isolates cultured during the study period were screened for the presence of NDM-1by PCR. Clinical characteristics of the NDM-1 positive isolates were studied and outcome of the patients was followed up. RESULTS: Of the 61 isolates, NDM-1 was detected in four isolates only. These were isolated from patients in the intensive care units and chest medicine ward. The source specimens were pus, sputum, bronchoalveolar lavage and endotracheal aspirate. The NDM-1 producers were susceptible only to polymyxin B. Only one patient responded to polymyxin B therapy, while the others succumbed to the infection. CONCLUSION: These findings reveal that NDM-1 is not a major mechanism mediating carbapenem resistance in P. aeruginosa in this centre. However, continuous surveillance and screening are necessary to prevent their dissemination.

The utility of IS6110 sequence based polymerase chain reaction in comparison to conventional methods in the diagnosis of extra-pulmonary tuberculosis
B Sekar, L Selvaraj, Alain Alexis, Sudharshan Ravi +2 more
2008· Indian Journal of Medical Microbiology38doi:10.4103/0255-0857.43575

IS6110 sequence based polymerase chain reaction (PCR) was compared with conventional bacteriological techniques in the laboratory diagnosis of extra-pulmonary tuberculosis (EPTB). One hundred and ninety one non-repeated clinical samples of EPTB and 17 samples from non-tuberculous cases as controls were included. All the samples were processed for Ziehl-Neelsen staining for acid fast bacilli (AFB) and 143 samples were processed by culture for M. tuberculosis . All the samples were processed for PCR amplification with primers targeting 123 bp fragment of insertion element IS6110 of M. tuberculosis complex. Of the total 191 samples processed, 34 (18%) were positive by smear for AFB. Culture for AFB was positive in 31(22%) samples among the 143 samples processed. Either smear or culture for AFB was found positive in 51(27%) samples. Of the total 191 samples processed 120 (63%) were positive by PCR. In 140 samples, wherein both the conventional techniques were found negative, 74 (53%) samples were positive by PCR alone. Among 51 samples positive by conventional techniques, 46 (90%) were found positive by PCR. PCR assay targeting IS6110 is useful in establishing the diagnosis of EPTB, where there is strong clinical suspicion, especially when the conventional techniques are negative.

High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions
Rosane M. B. Teles, Rose B. Teles, Thaís Porto Amadeu, Danielle F. Moura +4 more
2009· Infection and Immunity38doi:10.1128/iai.00896-09

ABSTRACT Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-α. It was observed that IFN-γ, TNF-α, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-α, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/ in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.

The significance of facial patches and Type I reaction for the development of facial nerve damage in leprosy. A retrospective study among 1226 paucibacillary leprosy patients
M Hogeweg, K. U. KIRAN, Sujai Suneetha
1991· Leprosy Review36doi:10.5935/0305-7518.19910016

Charts of 1226 paucibacillary leprosy patients, registered between 1982 and 1987 were reviewed for recent facial nerve damage, facial patches and the presence of Type I reaction. Twenty-six (2.1%) patients with recent lagophthalmos were identified. In a great majority (85%) patients with recent lagophthalmos showed significant patches over the malar region or around the eye, at the same side as the nerve damage together with clinical signs of Type I reaction. This combination of significant patches in certain locations and Type I reaction seems to be a pre-condition for facial nerve damage. The clinical implication is that a small group of patients may be identified, who are at risk of facial nerve damage. By examining these patients more carefully it will be possible to detect nerve damage early and to prevent permanent damage of the facial nerve by timely treatment with an appropriate steroid regimen.

Role of polymerase chain reaction in the diagnosis of early leprosy.
C. K. Job, J Jayakumar, Diana L. Williams, Thomas P. Gillis
1997· PubMed31

For 39 patients suspected of early leprosy, skin biopsies of the lesions were done and bisected. One piece was used for histopathologic examination and the other for polymerase chain reaction (PCR) studies to detect Mycobacterium leprae. The diagnosis of early leprosy was made clinically in 14 patients and by histopathologic study in 26 patients. Acid-fast bacilli were seen in the histopathologic sections of only two patients, and M. leprae were detected using PCR techniques in 11 patients. In one patient the diagnosis of leprosy was made only because of the detection of M. leprae in the PCR study. Since even in endemic countries the profile of leprosy is changing, detection of leprosy lesions in their early stages has become increasingly important. Since the finding of M. leprae is crucial in the confirmatory diagnosis of early leprosy, it is suggested that PCR studies to detect M. leprae be done wherever possible in conjunction with histopathologic examination. It is also recommended that the feasibility and the cost-effectiveness of both of these methods to find M. leprae be evaluated.

Within-host mathematical modeling on crucial inflammatory mediators and drug interventions in COVID-19 identifies combination therapy to be most effective and optimal
Bishal Chhetri, Vijay M. Bhagat, D. K. K. Vamsi, V. S. Ananth +4 more
2020· Alexandria Engineering Journal30doi:10.1016/j.aej.2020.12.011

The unprecedented Covid-19 pandemic has resulted in more than 14.75 million infections and 6, 10, 839 deaths in 212 countries. Appropriate interventions can decrease the rate of Covid-19 related mortality. Fast track clinical trials around the world are addressing the efficacy of individual pharmaceutical agent acting at various stages of pathogenesis. However, lessons learnt while dealing with past viral epidemics mandates, simultaneous use of such drugs in combination amongst different populations. Mathematical modelling studies can be extremely helpful in understanding the efficacy of drugs both individually and in combination. The current within-host mathematical model studies the natural history of Covid-19 in terms of complex interplay of virus replication and behaviour of host immune response. Additionally it studies the role of various drugs at various stages of pathogenesis. The model was validated by generating two-parameter heat plots, representing the characteristics of Covid-19, the sensitivity analysis identified the crucial parameters. The efficacy of interventions was assessed by optimal control problem. The model dynamics exhibited disease-free equilibrium and the infected equilibrium with their stability, based on the reproduction number R0, the transcritical bifurcation observed at R0=1. The burst rate and the natural death rate of the virus were observed as most significant parameters in the life-threatening Covid-19 pneumonia. The antiviral drugs affecting viral replication and those modulating the immune response, reduce the infected cells and viral load significantly. However, the yield was optimal and most effective when the combination therapy involving one or more antiviral and one or more immunomodulating drugs were administered together. These findings may help physicians with early decision making in treatment of life-threatening Covid-19 infection.

Prevalence of pulmonary tuberculosis among the tribal populations in India
Beena Thomas, Kannan Thiruvengadam, Chandrasekaran Vedhachalam, Adinarayanan Srividya +4 more
2021· PLoS ONE30doi:10.1371/journal.pone.0251519

IMPORTANCE: There is no concrete evidence on the burden of TB among the tribal populations across India except for few studies mainly conducted in Central India with a pooled estimation of 703/100,000 with a high degree of heterogeneity. OBJECTIVE: To estimate the prevalence of TB among the tribal populations in India. DESIGN, PARTICIPANTS, SETTING: A survey using a multistage cluster sampling design was conducted between April 2015 and March 2020 covering 88 villages (clusters) from districts with over 70% tribal majority populations in 17 States across 6 zones of India. The sample populations included individuals ≥15 years old. MAIN OUTCOME AND MEASURES: Eligible participants who were screened through an interview for symptoms suggestive of pulmonary TB (PTB); Two sputum specimens were examined by smear and culture. Prevalence was estimated after multiple imputations for non-coverage and a correction factor of 1.31 was then applied to account for non-inclusion of X-ray screening. RESULTS: A total of 74532 (81.0%) of the 92038 eligible individuals were screened; 2675 (3.6%) were found to have TB symptoms or h/o ATT. The overall prevalence of PTB was 432 per 100,000 populations. The PTB prevalence per 100,000 populations was highest 625 [95% CI: 496-754] in the central zone and least 153 [95% CI: 24-281] in the west zone. Among the 17 states that were covered in this study, Odisha recorded the highest prevalence of 803 [95% CI: 504-1101] and Jammu and Kashmir the lowest 127 [95% CI: 0-310] per 100,000 populations. Findings from multiple logistic regression analysis reflected that those aged 35 years and above, with BMI <18.5 Kgs /m2, h/o ATT, smoking, and/or consuming alcohol had a higher risk of bacteriologically positive PTB. Weight loss was relatively more important symptom associated with tuberculosis among this tribal populations followed by night sweats, blood in sputum, and fever. CONCLUSION AND RELEVANCE: The overall prevalence of PTB among tribal groups is higher than the general populations with a wide variation of prevalence of PTB among the tribal groups at zone and state levels. These findings call for strengthening of the TB control efforts in tribal areas to reduce TB prevalence through tribal community/site-specific intervention programs.