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Cureus Dec 2023Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated... (Review)
Review
Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated poorly and had to face discrimination due to the gruesome disease's complications. , the bacterium causative of leprosy, can generally be found in the nine-banded armadillo. The bacterium is transmitted via aerosol droplets and broken skin-to-skin contact. Once M enters the body, it will target peripheral nerves and the lining mucosa of the skin and eyes, thus causing inflammation and tenderness of the affected area. Over time, this will lead to peripheral neuropathy and weakness of the affected body parts. Treatment of leprosy involves multi-drug combinations such as dapsone, rifampin, and clofazimine. Even though leprosy is curable, early detection and treatment are crucial to preventing irreversible damage and disabilities. Prevention measures include early detection, treatment regimen adherence, close contact prophylaxis, contact tracing, and community awareness. This review aims to provide the latest diagnostic and therapeutic recommendations for leprosy. It outlines the epidemiology, microbiology, clinical treatment, and immunological methods used to detect leprosy.
PubMed: 38179342
DOI: 10.7759/cureus.49954 -
International Journal of... 2023A 35-year-old male patient with lepromatous leprosy came to the emergency room (ER) due to breathlessness and chest pain. The patient was diagnosed with pulmonary...
A 35-year-old male patient with lepromatous leprosy came to the emergency room (ER) due to breathlessness and chest pain. The patient was diagnosed with pulmonary tuberculosis (TB) after a bronchoscopy and started on antitubercular therapy. However, the patient continued to experience tachycardia and desaturation, and on further evaluation, Computed tomography pulmonary angiography revealed an embolus in the right descending pulmonary artery. The patient was found to have an elevated d-dimer. Further investigation revealed that the cause of the pulmonary thromboembolism (PTE) was the thalidomide medication that the patient was taking for type 2 leprosy reaction. The medication was stopped, and the patient was treated with low-molecular-weight heparin and discharged with apixaban for six months. The patient's condition improved on follow-up. This case is unique due to the rare combination of pulmonary TB, leprosy, and pulmonary embolism brought on by thalidomide administration. Physicians should be aware of the possibility of co-infection of TB and leprosy and the need to rule out thromboembolism when patients are on thalidomide.
Topics: Male; Humans; Adult; Mycobacterium leprae; Mycobacterium tuberculosis; Thalidomide; Coinfection; Leprosy; Pulmonary Embolism; Tuberculosis, Pulmonary
PubMed: 38149553
DOI: 10.4103/ijmy.ijmy_186_23 -
International Journal of... 2023Leprosy is still a global problem, especially in developing countries, including Indonesia. Ineffective prevention of leprosy leads to active transmission of the...
BACKGROUND
Leprosy is still a global problem, especially in developing countries, including Indonesia. Ineffective prevention of leprosy leads to active transmission of the disease. World Health Organization (WHO) recommend post-exposure prophylaxis (PEP) with single dose of rifampicin (SDR) for leprosy patients. Previous study showed protective effect of SDR against leprosy, especially for the first 2 years. Hence, the use of PEP and IgM anti PGL-1 examination are required to suspend the chain of leprosy transmission. This study evaluated the effectiveness of SDR administration by comparing IgM anti-PGL-1 antibody levels in seropositive household contacts before and after 2 years of SDR administration.
METHODS
Analytical observational laboratory study comparing IgM anti PGL-1 antibody levels before and after 2 years of SDR administration in leprosy contacts, with a prospective follow-up study design. We conducted this study from December 2022 to January 2023 at Dr. Mohammad Hoesin General Hospital Palembang. All seropositive household contacts of leprosy who had been administrated SDR 2 years ago were included, then PGL-1 antibody levels were examined.
RESULTS
The use of SDR showed significant improvement in leprosy contacts after 2 years (P=0.000). The median antibody level before SDR administration was 1,209.20 (615.81 - 4,353.60), which decrease to 146.03 (0 - 2,487.80) U/mL after 2 years. There was statistically significant relationship between history of BCG vaccination (P=0.003) and IgM PGL-1 antibody levels after 2 years of SDR administration.
CONCLUSION
There is a significant decrease in IgM anti PGL-1 antibody levels among leprosy contacts after 2 years of SDR chemoprophylaxis administration.
Topics: Humans; Rifampin; Post-Exposure Prophylaxis; Follow-Up Studies; Prospective Studies; Leprosy; Immunoglobulin M; Glycolipids; Mycobacterium leprae; Antibodies, Bacterial; Antigens, Bacterial
PubMed: 38149534
DOI: 10.4103/ijmy.ijmy_118_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 -
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 -
Cureus Nov 2023Leprosy reactions are acute exacerbations of the signs and symptoms of leprosy occurring during the natural course of the disease and during or after treatment. Left... (Review)
Review
Leprosy reactions are acute exacerbations of the signs and symptoms of leprosy occurring during the natural course of the disease and during or after treatment. Left untreated or improperly managed, reactions can lead to severe nerve function impairment and subsequently to disabilities. In the present context of leprosy eradication efforts, leprosy reactions continue to pose a significant and enduring challenge. Type 1 leprosy reaction and type 2 leprosy reaction are substantial contributors to nerve impairment and the subsequent development of enduring impairments. The study of immunopathogenesis of leprosy reactions has emerged as a significant area of research due to its potential to identify critical targets for the early detection and management of these episodes. This study aims to reveal the pathogenesis of type 1 and 2 leprosy reactions so that they can form the basis for their treatment. The study used scientific journals from reputable platforms such as PubMed, Scopus, and Google Scholar to evaluate the pathogenesis of leprosy reaction type 1 and 2 in leprosy patients. This review indicates that the progression of leprosy nerve damage and sensitivity to reactions may be predicted using genetic and serum markers in the human host. A more profound comprehension of the molecular processes underlying leprosy reactions may offer a logical plan for early detection and leprosy reaction complication prevention.
PubMed: 38130570
DOI: 10.7759/cureus.49155 -
Frontiers in Genetics 2023Leprosy is an infectious disease primarily caused by the obligate intracellular parasite . Although it has been considered eradicated in many countries, leprosy... (Review)
Review
Leprosy is an infectious disease primarily caused by the obligate intracellular parasite . Although it has been considered eradicated in many countries, leprosy continues to be a health issue in developing nations. Besides the social stigma associated with it, individuals affected by leprosy may experience nerve damage leading to physical disabilities if the disease is not properly treated or early diagnosed. Leprosy is recognized as a complex disease wherein socioenvironmental factors, immune response, and host genetics interact to contribute to its development. Recently, a new field of study called epigenetics has emerged, revealing that the immune response and other mechanisms related to infectious diseases can be influenced by noncoding RNAs. This review aims to summarize the significant advancements concerning non-coding RNAs in leprosy, discussing the key perspectives on this novel approach to comprehending the pathophysiology of the disease and identifying molecular markers. In our view, investigations on non-coding RNAs in leprosy hold promise and warrant increased attention from researches in this field.
PubMed: 38116294
DOI: 10.3389/fgene.2023.1295586 -
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 -
Le Infezioni in Medicina 2023Known before Christ and in ancient Egypt, leprosy was believed to be a mysterious disease of supernatural origin. It covered the body with lumps and sores, dulled the...
Known before Christ and in ancient Egypt, leprosy was believed to be a mysterious disease of supernatural origin. It covered the body with lumps and sores, dulled the senses, produced altered facial features and mutilation of the limbs. By the 6th century AD, the disease had certainly made its appearance in Western Europe and continued to occur in the following centuries. It was also thought to be attributable to poverty and poor sanitation. Leprosy was not considered an infectious disease until 1873, when physician G. H. A. Hansen first identified , calling it Hansen's bacillus, and the disease was named Hansen's disease. This paper analyses clinical reports on leprosy observed in Northern Italy, in the Comacchio area near Ferrara (Po Delta), in the 19th century, taking into consideration documents and manuscripts of the time. The scholars who made the greatest contribution to the description of the disease in and around Comacchio area were Antonio Campana, Andrea Verga, Alessandro Colla, Clodoveo Biagi, Ottone Schrön, Giacomo Sangalli, Raffaele Cavalieri, and local physicians Cristoforo Belloli, and Francesco Ballotta. Observations on the manifestations of the disease and attempts to cure it, including milk diet, are reported. In particular, this morbid form, which was not found in neighboring territories, was called "Mal di formica" because of its benignity at onset, its slowness and its slow progress. Tubercular Leprosy or Mal di fegato, a form of incurable leprosy was nothing more than the leprosy or elephantiasis described by the Greeks and Hebrews. The people most affected were women, who accounted for two-thirds of the sick. According to some authors, the causes of leprosy could be attributed to overuse of certain rotten or salted fish. Campana was the first to think that a lazaret should be erected for the sick.
PubMed: 38075412
DOI: 10.53854/liim-3104-19 -
Human Genomics Dec 2023In recent years, the mitochondria/immune system interaction has been proposed, so that variants of mitochondrial genome and levels of heteroplasmy might deregulate...
BACKGROUND
In recent years, the mitochondria/immune system interaction has been proposed, so that variants of mitochondrial genome and levels of heteroplasmy might deregulate important metabolic processes in fighting infections, such as leprosy.
METHODS
We sequenced the whole mitochondrial genome to investigate variants and heteroplasmy levels, considering patients with different clinical forms of leprosy and household contacts. After sequencing, a specific pipeline was used for preparation and bioinformatics analysis to select heteroplasmic variants.
RESULTS
We found 116 variants in at least two of the subtypes of the case group (Borderline Tuberculoid, Borderline Lepromatous, Lepromatous), suggesting a possible clinical significance to these variants. Notably, 15 variants were exclusively found in these three clinical forms, of which five variants stand out for being missense (m.3791T > C in MT-ND1, m.5317C > A in MT-ND2, m.8545G > A in MT-ATP8, m.9044T > C in MT-ATP6 and m.15837T > C in MT-CYB). In addition, we found 26 variants shared only by leprosy poles, of which two are characterized as missense (m.4248T > C in MT-ND1 and m.8027G > A in MT-CO2).
CONCLUSION
We found a significant number of variants and heteroplasmy levels in the leprosy patients from our cohort, as well as six genes that may influence leprosy susceptibility, suggesting for the first time that the mitogenome might be involved with the leprosy process, distinction of clinical forms and severity. Thus, future studies are needed to help understand the genetic consequences of these variants.
Topics: Humans; Heteroplasmy; Genome, Mitochondrial; Leprosy; Mitochondria
PubMed: 38062538
DOI: 10.1186/s40246-023-00555-8