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Indian Dermatology Online Journal 2023(MIP), previously called Mw vaccine, is a one-of-a-kind immunomodulatory vaccine. It was indigenously developed in India for use in leprosy. MIP is heat-killed which... (Review)
Review
(MIP), previously called Mw vaccine, is a one-of-a-kind immunomodulatory vaccine. It was indigenously developed in India for use in leprosy. MIP is heat-killed which is a non-pathogenic atypical mycobacterium belonging to Class IV of Runyon classification. It shares epitopes with and , which forms the rationale behind its use in leprosy and tuberculosis. MIP activates both innate and acquired immunity. It induces a Th1 and Th17 immune response along with downregulation of Th2 pathway and activates macrophages and dendritic cells. MIP vaccine is safe with adverse effects such as local site erythema, swelling, and rarely fever and other systemic reactions. Apart from leprosy, MIP has been used in dermatological diseases such as warts and psoriasis. Clinical trials have evaluated the efficacy of MIP in a plenitude of non-dermatological conditions such as category II tuberculosis, Gram-negative sepsis, non-small cell lung cancer, human immunodeficiency virus (HIV), muscle-invasive bladder cancer, and very recently, coronavirus 2019 (COVID-19). and animal studies have also demonstrated its utility in leishmaniasis, melanoma, and as a vaccine for the prevention of pregnancy. The PubMed database was searched using ", MIP, " as the keyword in title. This comprehensive review provides useful information for healthcare professionals about immunotherapeutic potential of MIP vaccine, its composition, dosing schedule, administration, and side effects besides its efficacy in various indications other than leprosy.
PubMed: 38099011
DOI: 10.4103/idoj.idoj_360_23 -
Pathogens (Basel, Switzerland) Dec 2023is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to... (Review)
Review
BACKGROUND
is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to mycobacterial antigens, classified as type1 (T1R), a predominant cellular immune response, or type2 (T2R), a humoral phenomenon, leading to a high number of bacilli in infected cells and nerve structures. Xenophagy is a type of selective autophagy that targets intracellular bacteria for lysosomal degradation; however, its immune mechanisms during leprosy reactions are still unclear. This review summarizes the relationship between the autophagic process and elimination during leprosy reactions.
METHODS
Three databases, PubMed/Medline (n = 91), Scopus (n = 73), and ScienceDirect (n = 124), were searched. After applying the eligibility criteria, articles were selected for independent peer reviewers in August 2023.
RESULTS
From a total of 288 studies retrieved, eight were included. In multibacillary (MB) patients who progressed to T1R, xenophagy blockade and increased inflammasome activation were observed, with IL-1β secretion before the reactional episode occurrence. On the other hand, recent data actually observed increased IL-15 levels before the reaction began, as well as IFN-γ production and xenophagy induction.
CONCLUSION
Our search results showed a dichotomy in the T1R development and their relationship with xenophagy. No T2R studies were found.
PubMed: 38133338
DOI: 10.3390/pathogens12121455 -
The Indian Journal of Medical Research Feb 2024Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a... (Review)
Review
Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a public health problem in 2005 in India, around 1.2 lakh cases have been detected every year over the last decade indicating active transmission of leprosy bacillus (Mycobacterium leprae). Single-nucleotide polymorphisms (SNPs), genomic insertions/deletions and variable-number tandem repeats (VNTRs) have been identified as genetic markers for tracking M. leprae transmission. As the leprosy bacilli cannot be cultured in vitro, molecular testing of M. leprae genotypes is done by polymerase chain reaction-based sequencing which provides a practical alternative for the identification of strains as well as drug resistance-associated mutations. Whole-genome sequencing (WGS) of M. leprae directly from clinical samples has also proven to be an effective tool for identifying genetic variations which can further help refine the molecular epidemiological schemes based on SNPs and VNTRs. However, the WGS data of M. leprae strains from India are scarce, being responsible for a gross under-representation of the genetic diversity of M. leprae strains present in India and need to be addressed suitably. Molecular studies of leprosy can provide better insight into phylogeographic markers to monitor the transmission dynamics and emergence of antimicrobial resistance. An improved understanding of M. leprae transmission is essential to guide efficient leprosy control strategies. Therefore, this review compiles and discusses the current status of molecular epidemiology, genotyping and the potential of genome-wide analysis of M. leprae strains in the Indian context.
Topics: Humans; DNA, Bacterial; Leprosy; Molecular Epidemiology; Mycobacterium leprae; Polymorphism, Single Nucleotide; India
PubMed: 38577854
DOI: 10.4103/ijmr.ijmr_2383_22 -
International Journal of... 2023Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although... (Observational Study)
Observational Study
BACKGROUND
Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand.
METHODS
The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019-December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test.
RESULTS
A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases.
CONCLUSION
Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority.
Topics: Female; Humans; Male; Bacillus; Drug Therapy, Combination; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prospective Studies; Socioeconomic Factors
PubMed: 37721229
DOI: 10.4103/ijmy.ijmy_108_23 -
International Journal of... 2023The lepromatous leprosy (LL) disease is caused by Mycobacterium leprae and Mycobacterium lepromatosis which is characterized by inadequate response to treatment, a...
BACKGROUND
The lepromatous leprosy (LL) disease is caused by Mycobacterium leprae and Mycobacterium lepromatosis which is characterized by inadequate response to treatment, a propensity to drug resistance, and patient disability. We aimed to evaluate current immunomodulatory medicines and their target proteins collectively as a drug repurposing strategy to decipher novel uses for LL.
METHODS
A dataset of human genes associated with LL-immune response was retrieved from public health genomic databases including the Human Genome Epidemiology Navigator and DisGeNET. Retrieved genes were filtered and enriched to set a robust network (≥10, up to 21 edges) and analyzed in the Cytoscape program (v3.9). Drug associations were obtained in the NDEx Integrated Query (v1.3.1) coupled with drug databases such as ChEMBL, BioGRID, and DrugBank. These networks were analyzed in Cytoscape with the CyNDEx-2 plugin and STRING protein network database.
RESULTS
Pathways analyses resulted in 100 candidate drugs organized into pharmacological groups with similar targets and filtered on 54 different drugs. Gene-target network analysis showed that the main druggable targets associated with LL were tumoral necrosis factor-alpha, interleukin-1B, and interferon-gamma. Consistently, glucosamine, binimetinib, talmapimod, dilmapimod, andrographolide, and VX-702 might have a possible beneficial effect coupled with LL treatment.
CONCLUSION
Based on our drug repurposing analysis, immunomodulatory drugs might have a promising potential to be explored further as therapeutic options or to alleviate symptoms in LL patients.
Topics: Humans; Leprosy, Lepromatous; Drug Repositioning; Mycobacterium leprae; Interferon-gamma
PubMed: 38149532
DOI: 10.4103/ijmy.ijmy_105_23 -
Infection, Genetics and Evolution :... Dec 2023Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Both organisms cannot be cultured in vitro. M. lepromatosis was found to be associated mainly...
BACKGROUND
Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Both organisms cannot be cultured in vitro. M. lepromatosis was found to be associated mainly with diffuse lepromatous leprosy and with Lucio's phenomena initially. Later, M. lepromatosis was observed in borderline leprosy cases (BL), lepromatous leprosy cases (LL) and leprosy reactional cases (T1R and ENL). Although many cases are being reported with similar clinical features like Lucio phenomenon in India but M. lepromatosis was not isolated from these cases. The aim of this study was to screen MB patients and patients with type 2 reaction for the presence of M. lepromatosis.
METHODOLOGY
We recruited a total of 75 multibacillary leprosy cases (45 MB cases without reaction and 30 type 2 reaction (ENL) cases) from TLM hospitals Purulia (West Bengal), Barabanki (Uttar Pradesh), Shahdara (Delhi) and PGIMER (Chandigarh), India. Punch biopsies of 5 mm were collected in 70% ethanol from all the study subjects. DNA was extracted followed by Hemi-nested PCR targeting 16S rRNA gene specific for M. lepromatosis. Further, PCR products were processed for Sanger sequencing for an absolute confirmation of M. lepromatosis. Whole genome sequencing was done to confirm the presence of M. lepromatosis.
RESULT
We observed presence of M. lepromatosis in 4 necrotic ENL patients by heminested PCR. There was 100% 16S rRNA sequence similarity with M. lepromatosis FJ924 in one case, 98.96% in two cases and in one case it was 90.9% similarity by nucleotide BLAST (BLASTn) by using the NCBI website. On the basis of Sanger sequencing, we noted presence of M. lepromatosis in 3 necrotic ENL patients as one sample only gave 90.9% similarity by BLASTn. On the basis of de novo assembly and genome obtained, only one sample S4 with a 2.9 mb genome size was qualified for downstream analysis. Sixteen M. lepromatosis- specific proteins were identified in this case and the closest species was M. lepromatosis strain FJ924 based on whole genome level phylogeny.
CONCLUSION
These results provide valuable insights into the prevalence of M. lepromatosis in ENL patients in different regions of India and contribute to our understanding of the genetic characteristics of this pathogen in the context of leprosy.
Topics: Humans; Leprosy, Lepromatous; RNA, Ribosomal, 16S; Mycobacterium leprae; Leprosy; Genomics
PubMed: 38056703
DOI: 10.1016/j.meegid.2023.105537 -
Cureus Apr 2024Leprosy is a great mimicker. It is caused by and , together termed the complex. Leprosy can result in systemic manifestations; however, the neurocutaneous syndrome is... (Review)
Review
Leprosy is a great mimicker. It is caused by and , together termed the complex. Leprosy can result in systemic manifestations; however, the neurocutaneous syndrome is the most classic. There is a gap in recognizing the condition leading to misdiagnosis and delays in treatment. Leprosy remains an important cause of aesthetic and functional impairment. In this paper, we provide a practical review of leprosy touching on pathophysiology, clinical manifestation, classification, diagnostic approach and management of the condition in a way that can translate into clinical practice and help physicians better identify and manage potential cases of leprosy.
PubMed: 38694670
DOI: 10.7759/cureus.57374 -
ACS Infectious Diseases Aug 2023Intra-household contacts (HCs) of leprosy patients are at increased risk of infection by and about ∼5-10% will develop active disease. A prognostic tool to identify...
Intra-household contacts (HCs) of leprosy patients are at increased risk of infection by and about ∼5-10% will develop active disease. A prognostic tool to identify HCs with the greatest risk of progressing to active disease would enhance early leprosy diagnosis and optimize prophylactic intervention. Previous metabolomics studies suggest that host lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are potential biomarkers for leprosy. In this study, we investigated retrospective sera of leprosy HCs by liquid chromatography-mass spectrometry and enzyme-linked immunoassay to determine whether circulating levels of ω-3 and ω-6 PUFA metabolites were altered in HCs that developed leprosy (HCDL) in comparison to those that did not (HCNDL). Sera were collected from HCs at the time of index case diagnosis and before clinical signs/symptoms of leprosy. Our findings showed that HCDL sera exhibited a distinct metabolic profile in comparison to HCDNL. Specifically, arachidonic acid, leukotriene B, 11-hydroxyeicosatetraenoic acid, prostaglandin D, and lipoxin A were elevated in HCDL. In contrast, prostaglandin E levels were reduced in HCDL. The ω-3 PUFAs, docosahexaenoic acid, eicosapentaenoic acid, and the docosahexaenoic acid-derived resolvin D1 and maresin-1 were also elevated in HCDL individuals compared to HCNDL. Principal component analyses provided further evidence that lipid mediators could serve as an early biomarker for progression to active leprosy. A logistic model identified resolvin D1 and D2, and prostaglandin D as having the greatest potential for early detection of HCs that will manifest leprosy.
Topics: Humans; Docosahexaenoic Acids; Mycobacterium leprae; Retrospective Studies; Fatty Acids, Unsaturated; Leprosy; Fatty Acids, Omega-3; Prostaglandins; Biomarkers
PubMed: 37428112
DOI: 10.1021/acsinfecdis.2c00585 -
Infection and Drug Resistance 2024Leprosy and tuberculosis are two of the oldest and most common mycobacterial infections, caused by and for leprosy and for tuberculosis. Dual infections have been...
BACKGROUND
Leprosy and tuberculosis are two of the oldest and most common mycobacterial infections, caused by and for leprosy and for tuberculosis. Dual infections have been known since ancient times; however, cases remain rarely reported in the literature, even in countries where both diseases are endemic, such as Madagascar.
PURPOSE
We report a case series of simultaneous occurrence of leprosy and tuberculosis.
PATIENTS AND METHODS
In this retrospective study, we reviewed the medical records of patients with leprosy registered at the Department of Dermatology, University Hospital Befelatanana, Antananarivo, Madagascar, between January 2012 and June 2021. Patients with leprosy and diagnosed as coinfected by tuberculosis were included in the study.
RESULTS
Of the 120 leprosy cases observed during the study period, coinfection with leprosy and tuberculosis was found in five patients. The mean age was 43.4 (SD 13.2) ranging, 21-59 years. Male gender was predominant (4/5). Four patients presented with lepromatous leprosy, and one with borderline lepromatous leprosy. Three patients experienced leprosy reaction. Four cases of pulmonary tuberculosis and one case of multifocal tuberculosis were observed. The diagnosis of leprosy preceded tuberculosis in four cases, and a coinfection diagnosis was made simultaneously in one case. The average time to develop tuberculosis was 38.8 (SD 10.2) months. HIV infection, malnutrition, alcohol consumption, and long-term corticosteroid therapy were the immunosuppressive factors reported in our patients. Three patients received concomitant multidrug therapy for leprosy and tuberculosis.
CONCLUSION
Dermatologists should be aware of the importance of screening patients affected by leprosy for latent or active tuberculosis to prevent morbidity and mortality due to coinfection and to reduce the risk of acquired resistance to rifampicin, which is the greatest risk of this association.
PubMed: 38645889
DOI: 10.2147/IDR.S458888 -
Current Biology : CB May 2024Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient...
Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease's evolutionary history, the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England. However, the time frame, distribution, and direction of transmissions remains unknown. Here, we studied 25 human and 12 squirrel samples from two archaeological sites in Winchester, a medieval English city well known for its leprosarium and connections to the fur trade. We reconstructed four medieval M. leprae genomes, including one from a red squirrel, at a 2.2-fold average coverage. Our analysis revealed a phylogenetic placement of all strains on branch 3 as well as a close relationship between the squirrel strain and one newly reconstructed medieval human strain. In particular, the medieval squirrel strain is more closely related to some medieval human strains from Winchester than to modern red squirrel strains from England, indicating a yet-undetected circulation of M. leprae in non-human hosts in the Middle Ages. Our study represents the first One Health approach for M. leprae in archaeology, which is centered around a medieval animal host strain, and highlights the future capability of such approaches to understand the disease's zoonotic past and current potential.
Topics: Animals; Mycobacterium leprae; Sciuridae; Leprosy; Humans; Genome, Bacterial; Phylogeny; England; DNA, Ancient; Archaeology; History, Medieval
PubMed: 38703773
DOI: 10.1016/j.cub.2024.04.006