Multidrug Resistant
            <i>Mycobacterium leprae</i>
            from Patients with Leprosy

Maeda, Shingo; Matsuoka, Masao; Nakata, Noboru; Kai, Masahiro; Maeda, Yosuke; Hashimoto, Ken; Kimura, Hiroaki; Kobayashi, Kazuo; Kashiwabara, Yoshiko

doi:10.1128/aac.45.12.3635-3639.2001

Cited by 134 publications

(123 citation statements)

References 16 publications

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“…It is alarming to find scientific reports on M. leprae cases with multiresistance to rifampicin, ofloxacin and dapsone, which, albeit few, ring an alarm about the possibility that one of the causes of therapeutic failure may be the presence of multiresistance (17)(18)(19).…”

mentioning

confidence: 99%

“…These changes are determined by mutations in the drug resistance-determining region (DRDR) in the folP1, rpoβ, and gyrA genes which have demonstrated to confer resistance to dapsone, rifampicin, and ofloxacin, respectively. By defining resistance mechanisms it is possible to use DNAbased assays, namely PCR-direct DNA sequencing or reverse hybridization to examine susceptibility to these drugs (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

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confidence: 99%

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¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación? Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

et al. 2013

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Introduction:There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. Objective: To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. Materials and methods: We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. Results: From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. Conclusions:The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.

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confidence: 99%

¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación? Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

et al. 2013

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“…Using this molecular biological techniques, many Dapsone resistance cases were reported from some Asian countries, 14,15,16 including Indonesia, 17,18 but the incidence was relatively low.…”

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confidence: 99%

“…From a molecular biology point of view, this type of mutation is relatively rare and should be paid more attention for preventing the spread of primary resistance to Dapsone. 20 Since the WHO-MDT regiment contains Dapsone for daily treatment, an alternative regiment should be anticipated for Dapsone resistant case.…”

Section: Discussionmentioning

confidence: 99%

DAPSONE RESISTANCE IN A Mycobacterium leprae ISOLATE WITH TWO POINT MUTATIONS IN folP GENE FROM A LEPROSY PATIENT

Ardiaty

Wahyuni

Prakoeswa

et al. 2016

IJTID

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“…The situation implies that there is a need to develop new vaccines and immunotherapeutic tools to control the disease. Moreover, there is increased concern about the disease due to the emergence of drug-resistant bacilli (16), complications due to severe reactions, and peripheral nerve injury due to the tropism of the bacilli to invade Schwann cells (13,20,24).…”

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confidence: 99%

Novel 33-Kilodalton Lipoprotein fromMycobacterium leprae

et al. 2002

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A novel Mycobacterium leprae lipoprotein LpK (accession no. ML0603) was identified from the genomic database. The 1,116-bp open reading frame encodes a 371-amino-acid precursor protein with an N-terminal signal sequence and a consensus motif for lipid conjugation. Expression of the protein, LpK, in Escherichia coli revealed a 33-kDa protein, and metabolic labeling experiments and globomycin treatment proved that the protein was lipidated. Fractionation of M. leprae demonstrated that this lipoprotein was a membrane protein of M. leprae. The purified lipoprotein was found to induce production of interleukin-12 in human peripheral blood monocytes. The studies imply that M. leprae LpK is involved in protective immunity against leprosy and may be a candidate for vaccine design.The aggressive global implementation of effective chemotherapy has resulted in a diminution of leprosy cases from ca. 10 million in 1985 to ca. 800,000 today (32, 33). However, the World Heath Organization (WHO) elimination goal has not yet been achieved, and there is no evidence as yet of a reduction in the number of new cases, in that, according to a WHO epidemiological survey, more than 650,000 new cases were detected globally at the beginning of 2000 (33). The situation implies that there is a need to develop new vaccines and immunotherapeutic tools to control the disease. Moreover, there is increased concern about the disease due to the emergence of drug-resistant bacilli (16), complications due to severe reactions, and peripheral nerve injury due to the tropism of the bacilli to invade Schwann cells (13,20,24).Mycobacterial entities involved in the sequelae of immunoregulatory events are not clear as yet. Recently, lipoproteins are reported to influence both innate and adaptive immunity (12,21). Since the process of lipid modification in murein lipoproteins occur only in prokaryotes (34), these proteins could be assumed to be useful in the regulation of bacterial infection.Bacterial lipoproteins containing N-acyl diglyceride-cysteine residues, flanked by characteristic amino acids motif that are required for posttranslational processing via the signal peptidase II (27, 34), have been extensively studied in gram-positive and gram-negative bacteria. The only two well-known mycobacterial lipoproteins are the 19-and 38-kDa lipoproteins of Mycobacterium tuberculosis (19,21,35). Another membrane located lipoprotein, reported by Sjosted et al. (29,30), is a 17-kDa Francisella tularensis lipoprotein that was found to be T-cell stimulatory. Borrelia burgdorferi and Treponema pallidum, the etiological agents of Lyme disease and syphilis, respectively, are known to possess abundant lipoproteins (23), which act as major antagonists with the ability to influence both innate and adaptive immune responses during infection (12). These lipoproteins are therefore presumed to be involved in the host responses, inducing interleukin-12 (IL-12) from the host cells. Since IL-12 has T-cell stimulatory properties, which in turn elicit the production of gamma inte...

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Multidrug Resistant Mycobacterium leprae from Patients with Leprosy

Cited by 134 publications

References 16 publications

¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación? Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación? Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

DAPSONE RESISTANCE IN A Mycobacterium leprae ISOLATE WITH TWO POINT MUTATIONS IN folP GENE FROM A LEPROSY PATIENT

Novel 33-Kilodalton Lipoprotein fromMycobacterium leprae

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