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2.
Mol Biol Rep ; 51(1): 504, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38616219

RESUMEN

BACKGROUND: Mycobacterium leprae causes leprosy that is highly stigmatized and chronic infectious skin disease. Only some diagnostic tools are being used for the identification M. leprae in clinical samples, such as bacillary detection, and histopathological tests. These methods are invasive and often have low sensitivity. Currently, the PCR technique has been used as an effective tool fordetecting M. leprae DNA across different clinical samples. The current study aims to detect M. leprae DNA in urine samples of untreated and treated leprosy patients using the Rlep gene (129 bp) and compared the detection among Ridley-Jopling Classification. METHODS: Clinical samples (Blood, Urine, and Slit Skin Smears (SSS)) were collected from leprosy and Non-leprosy patients. DNA extraction was performed using standard laboratory protocol and Conventional PCR was carried out for all samples using Rlep gene target and the amplicons of urine samples were sequenced by Sanger sequencing to confirm the Rlep gene target. RESULTS: The M. leprae DNA was successfully detected in all clinical samples across all types of leprosy among all the study groups using RLEP-PCR. Rlep gene target was able to detect the presence of M. leprae DNA in 79.17% of urine, 58.33% of blood, and 50% of SSS samples of untreated Smear-Negative leprosy patients. The statistical significant difference (p = 0.004) was observed between BI Negative (Slit Skin Smear test) and RLEP PCR positivity in urine samples of untreated leprosy group. CONCLUSION: The PCR positivity using Rlep gene target (129 bp) was highest in all clinical samples among the study groups, across all types of leprosy. Untreated tuberculoid and PNL leprosy patients showed the highest PCR positivity in urine samples, indicating its potential as a non-invasive diagnostic tool for leprosy and even for contact screening.


Asunto(s)
Bacillus , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Piel , Firmicutes , Reacción en Cadena de la Polimerasa
3.
Infect Drug Resist ; 17: 1507-1513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645889

RESUMEN

Background: Leprosy and tuberculosis are two of the oldest and most common mycobacterial infections, caused by Mycobacterium leprae and Mycobacteium lepramatosis for leprosy and Mycobacterium tuberculosis 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.

4.
Cureus ; 16(4): e58708, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38651088

RESUMEN

Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread but also to prevent physical and social complications and reduce the disease burden. Objectives The study aims to evaluate the factors that lead to a delayed leprosy diagnosis. Methods This study was conducted in the outpatient departments of Leprosy Control Institute and Hospital, Dhaka, Bangladesh, and at Medical College for Women and Hospital, Dhaka, Bangladesh, from March 2023 to June 2023. A total number of 252 male (148) and female (104) patients were selected with any sign of leprosy, including disability, age ranging from 15 to 74 years. Data was collected in a pre-designed structured questionnaire by the researchers. To assess the risk of independent exposures of Grade 2 leprosy disabilities, we used a logistic regression model. A chi-square test showed the association between significant effects and leprosy disabilities. A p-value of 0.05 was considered as significant. For statistical analysis, STATA version 15 (StataCorp LLC, College Station, Texas, USA) was used. Results The study participants exhibited a higher percentage of disability, with a rate of 25.8% for Grade 2 disabilities. In addition to this, males represented a more considerable proportion, 58.7%, than females among leprosy and disability patients across all levels of disability. In our study, lack of money and painless symptoms showed a significant association (p<0.001) with Grade 2 disability. Conclusion The study reveals that Grade 2 disabilities are more common in males and are particularly prevalent in lower socioeconomic groups.

5.
Trop Med Infect Dis ; 9(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38535882

RESUMEN

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, an SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases retrospectively (2010-2017) and prospectively (2018-2022). We conducted a retrospective audit to determine the comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,641 household contacts were identified (9791 in the retrospective and 3850 in the prospective cohort). In the retrospective cohort, 1044 (11%) contacts were absent, 403 (4%) were ineligible for SDR, and 42 new cases were detected (0.4%) Overall, SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR, and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were 23 SDR refusals. The median time to SDR administration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts, respectively. SDR was readily accepted in both cohorts. The new case detection rate (0.5%) is consistent with that in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

6.
Acta Neurol Belg ; 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38438636

RESUMEN

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

7.
Front Public Health ; 12: 1148705, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38327578

RESUMEN

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.


Asunto(s)
COVID-19 , Lepra , Humanos , Mycobacterium leprae/genética , Pandemias , ADN Bacteriano/genética , COVID-19/epidemiología , Lepra/epidemiología , Lepra/microbiología , China/epidemiología
8.
9.
Cureus ; 16(1): e52784, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38389642

RESUMEN

Background Acid-fast bacilli Mycobacterium tuberculosis and Mycobacterium leprae are the causative organisms behind two major diseases of developing nations, tuberculosis and leprosy, respectively. To efficiently tackle these diseases in developing nations, drugs must be augmented with improved detection modalities. This necessitates the development of enhanced tools that can aid the current detection modalities being used in high-incidence areas. A no-code artificial intelligence model based on image classification is one such tool that can be used in the identification of acid-fast bacilli. This study utilizes three such no-code artificial intelligence models that originate from three different platforms but share identical training, testing, and subsequent evaluation. Thereafter, the study is directed at comparing the three models created and identifying the one that can function as a promising support system for the detection of acid-fast bacilli. Methods To begin with, a total of 1000 images per class, i.e., positive and negative for each disease, were captured from the diagnosed slides of tuberculosis and leprosy, taken from the Department of Pathology. Subsequently, these slides were reviewed again by a pathologist to demarcate them as positive or negative for acid-fast bacilli. Once the required number of images was captured, 600 images of each class were selected as the training set, 300 images as the testing set, and the remaining 100 images as the evaluation set. Data augmentation was then performed using techniques such as rotating, mirroring, cropping, and position shifting. These designated data sets were then used to train the image classification software available on the following three platforms: Lobe (Microsoft Corporation, Redmond, Washington, United States), Create ML (Apple Inc., Cupertino, California, United States), Python-based open-source software (PerceptiLabs, Stockholm, Sweden). The final evaluation was based on different parameters such as sensitivity, specificity, ease of use, learning curve, technological resources required, and feasibility of implementation. All parameters put together served the purpose of comparison to identify the most promising model. Results Out of the three models tested, the one built using Lobe is the most promising in terms of the evaluation parameters considered. For tuberculosis, the sensitivity and specificity values obtained were 96% each, while for leprosy, they were 100% and 96%, respectively. Also, the model built using Lobe had a near-negligible learning curve, in addition to being the most cost-effective and feasible model to implement. Furthermore, it had a unique real-time training feature, which constantly improved the model throughout the testing period, till the final sensitivity and specificity values were achieved. Conclusions In clinical situations where a high number of cases are encountered each day, a no-code artificial intelligence model built using Lobe would get exposed to a huge database, getting trained in real time. Subsequently, such a model would reach considerable levels of sensitivity and specificity and in turn, act as a promising support system for the detection of acid-fast bacilli.

10.
Acta Med Port ; 37(3): 215-219, 2024 Mar 01.
Artículo en Portugués | MEDLINE | ID: mdl-38271690

RESUMEN

Hansen's disease, commonly known as leprosy, is an infectious disease caused by Mycobacterium leprae. Being rare in developed countries, it is an increasingly common imported disease due to the migratory flow from countries where it is endemic. We present the case of a 21-year-old man who went to the emergency department with complaints of additive polyarthralgia involving large joints, papules, and erythematous plaques on the limbs with bullae and central necrosis and fever with chills for one week. Skin biopsy was performed revealing neutrophilic infiltrate with perineural granulomas. The bacilloscopy detected acid-alcohol resistant bacilli. The diagnosis of multibacillary HD with type 2 lepromatous reaction (erythema nodosum leprosum - ENL) was established, showing clinical improvement under corticosteroid therapy. ENL usually presents with painful lesions, being an atypical presentation of leprosy, especially in the presence of bullae and necrosis, making diagnosis difficult and challenging. Social stigma is often present making it difficult to accept the disease as well as adherence to treatment.


A doença de Hansen, vulgarmente conhecida como lepra, é uma doença infecciosa causada por Mycobacterium leprae. Sendo rara nos países desenvolvidos, configura uma doença de importação cada vez mais frequente considerando o fluxo migratório de países onde é endémica. Apresentamos o caso de um homem de 21 anos que recorreu ao serviço de urgência por poliartralgias de caráter aditivo envolvendo grandes articulações, pápulas e placas eritematosas nos membros com bolhas e necrose central e febre com calafrio com uma semana de evolução. Foi realizada biópsia cutânea que revelou infiltrado neutrofílico com granulomas de distribuição perineural e baciloscopia com deteção de bacilos ácido-álcool resistentes. Foi estabelecido o diagnóstico de DH multibacilar com reação lepromatosa tipo 2 (eritema nodoso leproso), apresentando melhoria clínica sob corticoterapia. O eritema nodoso leproso cursa habitualmente com lesões dolorosas, configurando uma apresentação atípica de lepra, sobretudo na presença de bolhas e necrose, tornando este diagnóstico altamente desafiante. O estigma social é frequentemente limitativo na aceitação da doença e adesão ao tratamento.


Asunto(s)
Eritema Nudoso , Lepra , Masculino , Humanos , Adulto Joven , Adulto , Vesícula , Lepra/tratamiento farmacológico , Lepra/epidemiología , Lepra/patología , Piel/patología , Eritema Nudoso/diagnóstico , Eritema Nudoso/tratamiento farmacológico , Eritema Nudoso/patología , Necrosis/patología
11.
ACS Infect Dis ; 10(2): 251-269, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38295025

RESUMEN

In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, Mycobacterium leprae and Mycobacterium ulcerans, are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.


Asunto(s)
Úlcera de Buruli , Mycobacterium ulcerans , Mycobacterium , Humanos , Mycobacterium leprae , Úlcera de Buruli/tratamiento farmacológico , Úlcera de Buruli/microbiología , Úlcera de Buruli/patología
12.
Artículo en Inglés | MEDLINE | ID: mdl-37070443

RESUMEN

Leprosy, often known as Hansen's disease is a contagious chronic infectious disease caused by Mycobacterium leprae (M. leprae). Our methodology is easily repeatable in tertiary care settings with diagnostic accuracy resources and staff capable of building a stewardship team. Comprehensive antimicrobial policies and programmes are required to properly alleviate the initial issue.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Lepra , Humanos , Lepra/tratamiento farmacológico , Mycobacterium leprae , Academias e Institutos , Atención a la Salud
13.
Protein Pept Lett ; 31(1): 11-24, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37962043

RESUMEN

The bacterial cell wall is composed of a wide variety of intricate proteins in addition to lipids, glycolipids, and polymers. Given the diversity of cell wall proteins among bacterial species, they are a feasible target for biomarker identification and characterization in clinical research and diagnosis of the disease. The slow growth rate of Mycobacterium leprae poses a major hurdle in the accurate diagnosis of leprosy before the onset of peripheral neuropathy. The use of biomarker- based diagnostic methods can help in preventing the spread and manifestation of leprosy. Despite many advances in research methods and techniques, there remains a knowledge gap regarding the cell wall proteomes of M. leprae that can be used as biomarkers. The cell wall and secretory proteins of M. leprae are the major focus of this review article. This article enfolds the characteristics and functions of M. leprae cell wall proteins and gives an insight into those cell wall proteins that are yet to be established as biomarkers. Tools and techniques used in cell wall extraction and biomarker identification can also be explored in this article.

14.
Trans R Soc Trop Med Hyg ; 118(3): 148-159, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-37850518

RESUMEN

BACKGROUND: This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist. RESULTS: A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients. CONCLUSIONS: This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.


Asunto(s)
Lepra , Humanos , Lepra/complicaciones , Lepra/diagnóstico , Sistema Nervioso Central/diagnóstico por imagen , Mycobacterium leprae , Encéfalo , Estudios de Cohortes
16.
J Infect Chemother ; 30(6): 531-535, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38141720

RESUMEN

INTRODUCTION: The importance of DNA repair enzymes in maintaining genomic integrity is highlighted by the hypothesis that DNA damage by reactive oxygen/nitrogen species produced inside the host cell is essential for the mutagenesis process. Endonuclease III (Nth), formamidopyrimide (Fpg) and endonuclease VIII (Nei) DNA glycosylases are essential components of the bacterial base excision repair process. Mycobacterium leprae lost both fpg/nei genes during the reductive evolution event and only has the nth (ML2301) gene. This study aims to characterize the mutations in the nth gene of M. leprae strains and explore its correlation with drug-resistance. METHOD: A total of 91 M. leprae positive DNA samples extracted from skin biopsy samples of newly diagnosed leprosy patients from NSCB Hospital Jabalpur were assessed for the nth gene as well as drug resistance-associated loci of the rpoB, gyrA and folP1 genes through PCR followed by Sanger sequencing. RESULTS: Of these 91 patients, a total of two insertion frameshift mutations, two synonymous and seven nonsynonymous mutations were found in nth in seven samples. Sixteen samples were found to be resistant to ofloxacin and one was found to be dapsone resistant as per the known DRDR mutations. No mutations were found in the rpoB region. Interestingly, none of the nth mutations were identified in the drug-resistant associated samples. CONCLUSION: The in-silico structural analysis of the non-synonymous mutations in the Nth predicted five of them were to be deleterious. Our results suggest that the mutations in the nth gene may be potential markers for phylogenetic and epidemiological studies.


Asunto(s)
Lepra , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Leprostáticos/farmacología , Leprostáticos/uso terapéutico , Lepra/genética , Lepra/tratamiento farmacológico , Filogenia , Farmacorresistencia Bacteriana/genética , Mutación , ADN Bacteriano/genética , India , Reparación del ADN/genética
17.
Acta Trop ; 249: 107019, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37952867

RESUMEN

INTRODUCTION: Leprosy is a chronic infectious disease that still persists as a public health problem in Brazil. Plantar ulcers are serious complications due to leprosy neuropathy and intensify the isolation and stigma of these individuals. The difficulty in closing these lesions associated with the fetid odor negatively impact the quality of life of people with these lesions. OBJECTIVE: To evaluate the clinical, socioeconomic conditions, degree of satisfaction and quality of life (QoL) of patients after healing of chronic ulcers on feet submitted to orthopedic surgery. METHODOLOGY: This is a qualitative, exploratory, descriptive and observational study carried out with 92 people after surgical treatment of chronic leprosy plantar ulcers. These patients were submitted to a semi-structured questionnaire raising questions of an epidemiological, socioeconomic and perception of quality-of-life order, comparing before and after the surgical procedure. RESULTS: Decrease in indicators - alcohol consumption, tobacco consumption, average monthly cost of analgesic medications, fetid wound odor, foot pain and number of dressings performed weekly; Recurrence of lesions in 55.4 % of cases, related to irregular use or lack of shoes and insoles; Improvement in self-perception of Quality of Life (QoL) in 89.1 % of patients after surgery. CONCLUSION: Orthopedic surgical treatment with resection of plantar bony prominences and skin grafting is an effective therapeutic method for closing chronic plantar ulcers in leprosy, resulting in a decrease in the financial costs employed and in an important improvement in the Quality-of-Life parameters of the individuals undergoing to this procedure. The availability and regular use of shoes and insoles is crucial to prevent recurrence of these injuries.


Asunto(s)
Úlcera del Pie , Lepra , Procedimientos Ortopédicos , Humanos , Úlcera del Pie/cirugía , Úlcera del Pie/etiología , Úlcera del Pie/prevención & control , Calidad de Vida , Lepra/complicaciones , Lepra/cirugía , Procedimientos Ortopédicos/efectos adversos , Cicatrización de Heridas
18.
Hum Genomics ; 17(1): 110, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38062538

RESUMEN

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.


Asunto(s)
Genoma Mitocondrial , Lepra , Humanos , Heteroplasmia , Genoma Mitocondrial/genética , Lepra/genética , Mitocondrias/genética
19.
Cureus ; 15(11): e49155, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38130570

RESUMEN

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.

20.
Front Genet ; 14: 1295586, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116294

RESUMEN

Leprosy is an infectious disease primarily caused by the obligate intracellular parasite Mycobacterium leprae. 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.

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