Unique TTC repeat base pair loss mutation in cases of pure neural leprosy: A survival strategy of Mycobacterium leprae?

De, Abhishek; Reja, Abu Hena Hasanoor; Biswas, Supratik; Bhattacharya, Basudev; Chatterjee, Gobinda; Basu, Keya; Sarda, Aarti; Chowdhury, Nidhi

doi:10.4103/0019-5154.160478

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…Given delays in the diagnosis of multibacillary (MB) leprosy, transmission of M. leprae from infected individuals to their contacts continues, and in many cases, irreversible nerve damage occurs before those infected are registered as patients [ 3 , 4 ]. It is remarkable that DNA amplification methods have been used for genomic studies and resistance-associated gene mutations [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

High frequency of M. leprae DNA detection in asymptomatic household contacts

et al. 2018

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BackgroundCharacterization of the Mycobacterium leprae genome has made possible the development of Polymerase Chain Reaction (PCR) systems that can amplify different genomic regions. Increased reliability and technical efficiency of quantitative PCR (qPCR) makes it a promising tool for early diagnosis of leprosy. Index cases that are multibacillary spread the bacillus silently, even before they are clinically diagnosed. Early detection and treatment could prevent transmission in endemic areas.MethodsIn this study, the qPCR technique is used to detect DNA of M. leprae in samples of slit skin smears (SSS) of the ear lobe and blood of leprosy patients and their asymptomatic household contacts residing in Governador Valadares, MG, Brazil, a hyperendemic area for leprosy. A total of 164 subjects participated in the study: 43 index cases, 113 household contacts, and, as negative controls, 8 individuals who reported no contact with patients nor history of leprosy in the family. The qPCR was performed to amplify 16S rRNA fragments and was specifically designed for M. leprae.ResultsOf asymptomatic household contacts, 23.89% showed bacillary DNA by qPCR in samples of SSS and blood. Also, 48.84% of patients diagnosed with leprosy were positive for qPCR while the bacillary load was positive in only 30.23% of patients. It is important to note that most patients were already receiving treatment when the collection of biological material for qPCR was performed. The level of bacillary DNA from household contacts was similar to the DNA levels detected in the group of paucibacillary patients.ConclusionConsidering that household contacts comprise a recognizable group of individuals with a high risk of disease, as they live in close proximity to a source of infection, qPCR can be used to estimate the risk of progress towards leprosy among household contacts and as a routine screening method for a chemoprophylactic protocol.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3056-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

High frequency of M. leprae DNA detection in asymptomatic household contacts

et al. 2018

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“…However, nerve biopsy being the major deterrent in our efforts to diagnose PNL, we had conducted a pilot study where we demonstrated M. Leprae DNA in specimens obtained out of FNA done on affected peripheral nerves in 13 patients. [ 3 4 ] FNA, being a relatively less invasive and simpler procedure, could be done with ease in our outpatient set up. The diagnostic yield of FNAC-PCR was as high as 84.6% in the pilot study.…”

Section: Discussionmentioning

confidence: 99%

“…In an effort to find a simple yet objective and test to diagnose PNL, the authors demonstrated in a pilot study that fine needle aspiration cytology (FNAC) when combined with Ziehl-Neelsen (ZN) staining and PCR gives a good diagnostic yield. [ 3 4 ] FNAC being a less invasive test needs less skill and infrastructure and comes with lesser rates of complications and can be easily performed within the existing infrastructure. With this background and in pursuit of further evidence, the authors conducted this study over a larger sample size, for a longer duration to determine the reliability, efficacy, and reproducibility of FNAC combined with ZN staining and PCR in diagnosis of PNL.…”

Section: Introductionmentioning

confidence: 99%

Use of fine needle aspirate from peripheral nerves of pure-neural leprosy for cytology and polymerase chain reaction to confirm the diagnosis: A follow-up study of 4 years

Reja

Aggarwal

et al. 2017

Indian J Dermatol

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Background:Pure neural leprosy (PNL) still remains a diagnostic challenge because of the absence of sine qua non skin lesions of leprosy and a confirmatory diagnostic method. The authors had earlier described a simple yet objective technique of combining fine needle aspiration cytology (FNAC) coupled with a multiplex polymerase chain reaction (PCR) in a pilot study, wherein the technique showed promise of a reliable diagnostic tool. In the pursuit of further evidence, the authors carried out a 4-year study with PNL cases to find the efficacy and reliability of the said method in a larger sample size.Aim:This study was conducted to find the efficacy, reliability, and reproducibility of FNAC coupled with multiplex PCR and Ziehl-Neelsen (ZN) staining in identifying the cases of PNL.Materials and Methods:All cases that were suspected to be suffering from PNL, following evaluation by two independent observers were included in the study and were subjected to FNAC from the affected nerve, and the aspirates were evaluated for cytology, ZN staining, and multiplex PCR for Mycobacterium leprae genome. In addition, serum anti-PGL1 levels were also performed in all the study subjects. Fifteen non-PNL cases were also included in the control arm.Results:A total of 47 cases were included in the test arm and subjected to FNAC. Conventional ZN staining could demonstrate acid-fast bacilli (AFB) in only 15 out of 47 cases (31.91%) while M. leprae DNA could be elicited in 37 (78.72%) cases by the multiplex PCR. Only 13 (27.65%) out of 47 cases showed anti-PGLI-1 antibody positivity. On cytological examination of the nerve aspirates, only 11 (23.40%) cases showed epithelioid cells whereas nonspecific inflammation was seen in 26 (75.60%) cases.Conclusion:The results of this study conducted over a larger sample size corroborate with the findings of our pilot study. In a resource poor set up, FNAC in combination with ZN staining and multiplex PCR is a rapid, simple, and easily performed test, which can give a reproducible and objective diagnosis in cases of PNL.

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“…NLRs, nucleotide-binding oligomerization domain (NOD)-like receptors are intracellular PRMs that, like TLRs, recognize and react to MAMPs or DAMPs in the cytosol, as per recent research in mammalian systems. [ 2 3 4 5 6 ]…”

Section: Introductionmentioning

confidence: 99%

A Cross-Sectional Study to Evaluate the Role of the Nuclear Factor Kappa B (Nf-κB) Pathway in Regulating the Cytokine Cascade and as a Potential Therapeutic Target in Leprosy

Hasanoor Reja,

De,

Chakraborty

et al. 2024

Indian Journal of Dermatology

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Pattern recognition receptors (PRRs), which are found in microorganisms but not in hosts, allow Leprae bacilli to be recognized as foreign. Several kinds of pattern recognition receptors, such as toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-1-like receptors (RLRs), are present in the innate immune system. Sen and Baltimore (1986) discovered the transcription factor nuclear factor kappa-B (NF-B), employed by eukaryotic cells to regulate immunity, cell differentiation and proliferation. This study aimed to evaluate the role of the nuclear factor kappa B (NF-B) pathway in controlling the cytokine cascade in leprosy due to a lack of understanding of the link between cytokines and the severity of leprosy. Clinically suspected Hansen’s patients were analysed for 4 years. Newly diagnosed leprosy patients were considered to have leprosy disease control (LDC). The cases with active or new lesions and an increase in BI by at least 2+, 12 months after completion of MDT were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (HC). An ELISA was performed to measure the concentration of five human cytokines. By qRT-PCR, the quantitative expression of receptor genes (NOD1 and NOD2), cytokine genes and the expression of the transcription factor NFκβ were evaluated. This was followed by a transcription factor NFκβ assay to see its expression in the monocytes of study subjects. Nuclear factor NF-κβ was found to have a pronounced response in monocytes of HC and LDC patients and LDR cases when treated with NOD1 and NOD2 ligands. Our study concludes that the NF-kB pathway is involved in the induction and regulation of the cytokine cascade that contributes to chronic inflammation in leprosy.

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Unique TTC repeat base pair loss mutation in cases of pure neural leprosy: A survival strategy of Mycobacterium leprae?

Cited by 5 publications

References 9 publications

High frequency of M. leprae DNA detection in asymptomatic household contacts

High frequency of M. leprae DNA detection in asymptomatic household contacts

Use of fine needle aspirate from peripheral nerves of pure-neural leprosy for cytology and polymerase chain reaction to confirm the diagnosis: A follow-up study of 4 years

A Cross-Sectional Study to Evaluate the Role of the Nuclear Factor Kappa B (Nf-κB) Pathway in Regulating the Cytokine Cascade and as a Potential Therapeutic Target in Leprosy

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