Molecular Detection of Rifampin and Ofloxacin Resistance for Patients Who Experience Relapse of Multibacillary Leprosy

Cambau, Emmanuelle; Bonnafous, Pascale; Evelyne, Perani; Sougakoff, Wladimir; Ji, Baohong; Jarlier, Vincent

doi:10.1086/324623

Cited by 74 publications

(34 citation statements)

References 24 publications

(44 reference statements)

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“…Rifampicin blocks transcription. The most commonly found mutation in the RRDR is Ser425Leu [45,47,53–56]. Out of many thousands of rifampicin-susceptible isolates, none harbored mutations at the RRDR locus in rpoB .…”

Section: Drug Resistancementioning

confidence: 99%

Mycobacterium Leprae : Genes, Pseudogenes And Genetic Diversity

Singh

Cole²

2010

Future Microbiol.

110

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Leprosy, which has afflicted human populations for millenia, results from infection with Mycobacterium leprae, an unculturable pathogen with an exceptionally long generation time. Considerable insight into the biology and drug resistance of the leprosy bacillus has been obtained from genomics. M. leprae has undergone reductive evolution and pseudogenes now occupy half of its genome. Comparative genomics of four different strains revealed remarkable conservation of the genome (99.995% identity) yet uncovered 215 polymorphic sites, mainly single nucleotide polymorphisms, and a handful of new pseudogenes. Mapping these polymorphisms in a large panel of strains defined 16 single nucleotide polymorphism-subtypes that showed strong geographical associations and helped retrace the evolution of M. leprae.

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Section: Drug Resistancementioning

confidence: 99%

Mycobacterium Leprae : Genes, Pseudogenes And Genetic Diversity

Singh

Cole²

2010

Future Microbiol.

110

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“…Although the number of multidrug-resistant strains is small, their occurrence is indeed an alarm bell and must be closely scrutinized. [33–35] In a recent study, across three countries it was found that from new cases 3% were dapsone-resistant and 2% were rifampicin-resistant. In samples from relapsed patients, 15% were dapsone-resistant and 8% were rifampicin-resistant.…”

Section: Who Therapy and Its Impactmentioning

confidence: 99%

Leprosy therapy, past and present: Can we hope to eliminate it?

Prasad

Kaviarasan

2010

Indian J Dermatol

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Leprosy remains an important problem globally. Timely detection of new cases and prompt treatment with MDT continue to be the main intervention strategies. We review the various issues related to classification, treatment, drug resistance and the possible steps to eliminate the disease in the near future. The need for newer anti leprosy agents has been felt and various agents like fluroquinolones, macrolides and minocycline have all been tried in various combinations and duration. Uniform MDT in all leprosy patients might be a logical one too. Drug resistance can be identified by PCR based DNA sequence analysis which saves much time. Drugs like thalidomide analogues, pentoxifylline, selective cytokine inhibitory drugs have proved effective in controlling type-2 reaction in leprosy patients. New drugs for leprosy reactions are still needed. Far from being eliminated as a public health problem, leprosy still causes a considerable long term morbidity in both developing and developed world. New treatment and the optimal length of MDT requires further research. We need genome based technology to address the unresolved issues of transmission of M. leprae.

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“…Molecular techniques using PCR technology and serological tests were developed; however, specificity and sensitivity were limited (11,(14)(15)(16)(17)(18)21). In this context, the identification of biomarkers that allow early diagnosis of leprosy and differentiation between forms of the disease with an adequate sensitivity and specificity is still required.…”

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confidence: 99%

Characterization of MicroRNA Expression Profiles and Identification of Potential Biomarkers in Leprosy

et al. 2017

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Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.KEYWORDS biomarker, leprosy, miRNA L eprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The infection affects primarily the skin and can cause damage to peripheral nerves, mucosa, and other organs, including liver and eyes. Leprosy is classified as a neglected tropical disease and remains one of the main causes of disability in the world (1-3). According to a World Health Organization (WHO) report including data from 138 countries, 211,974 newly diagnosed patients were notified in the year 2015 and 96% of them were reported from 22 countries, including Brazil (4).Leprosy presents a spectrum of clinical manifestations depending on the host immune response against M. leprae. It can be classified according to histopathological (Ridley-Jopling) criteria into different forms across two opposing poles: a so-called resistance pole responsible for a localized form of the disease (tuberculoid tuberculoid [TT]) and a susceptibility pole that is a disseminated form, which leads to the development of more severe clinical manifestations (lepromatous leprosy [LL]). There are also three intermediate and unstable forms: borderline tuberculoid (BT), borderline

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Molecular Detection of Rifampin and Ofloxacin Resistance for Patients Who Experience Relapse of Multibacillary Leprosy

Cited by 74 publications

References 24 publications

Mycobacterium Leprae : Genes, Pseudogenes And Genetic Diversity

Mycobacterium Leprae : Genes, Pseudogenes And Genetic Diversity

Leprosy therapy, past and present: Can we hope to eliminate it?

Characterization of MicroRNA Expression Profiles and Identification of Potential Biomarkers in Leprosy

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