A Second Case of Multidrug-resistant Mycobacterium leprae Isolated from a Japanese Patient with Relapsed Lepromatous Leprosy

Matsuoka, Masao; Kashiwabara, Yoshiko; Zhang, Liangfen; Goto, Masamichi; Kitajima, Shinichi

doi:10.1489/1544-581x(2003)71<240:ascomm>2.0.co;2

Cited by 38 publications

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“…Therefore, relapse has not been considered a problem, and organization of studies of this disease characteristic was somewhat neglected, leading to the recent WHO initiative to organize a resistance surveillance project for relapse cases, 26 years after having started MDT. This was possible due to the development and standardization of molecular genotyping procedures of genes associated with drug resistance (5,16,23,24,38,39). After the introduction of relapse surveillance by the WHO, many of the countries of endemicity reported leprosy relapses.…”

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confidence: 99%

Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

et al. 2012

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h Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P ‫؍‬ 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary. There is no doubt about the efficiency of the currently used multidrug therapy (MDT) scheme for treatment of leprosy, as demonstrated by the strong decrease in disease prevalence since its implementation and the low number of reported relapse cases (18). However, there has been a scarcity of in-depth studies of relapse occurrences in recent decades (27). As is known, differentiating diagnosis of relapse and reactional states poses some difficulties in the field, being responsible for under-or overdiagnosis of both disease stages. This is important because undiagnosed relapse cases could contribute to continuing disease transmission. In addition, hardly any data on the contribution of emergence of drug-resistant strains of Mycobacterium leprae to leprosy relapses exist.Diaminodiphenylsulfone (DDS), also called dapsone, was the first drug to be effective against leprosy worldwide, and the first cases of resistance to dapsone were detected in 1964 and involved two single nucleotide polymorphisms (SNPs) in the gene folP1, located in codons 53 and 55 (8, 9, 14, 29). Rifampin is the key component of the standard multidrug regimen used for treatment of leprosy, and it has been shown that PCR-based DNA sequence analysis of the rpoB gene of M. leprae was in full concordance with rifampin susceptibility testing in the mouse footpad system (17, 30). In addition to dapsone and rifampin, ofloxacin is also used for leprosy treatment and is a quinolone with an action mechanism based on interaction with DNA gyrase (2); SNPs in gyrA and gyrB confer resistance or hypersensitivity to quinolones (15). Although there is not yet an official definition of multidrug resistance (MDR) in leprosy, in parallel with tuberculosis, we adopt this terminology when we encounter resistance to rifampin and one other drug of the standard M...

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confidence: 99%

Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

et al. 2012

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“…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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¿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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“…10 There have also been various recently reported cases of multidrug-resistant strains of M. leprae. 16,[22][23][24][25] Despite the success of WHO-MDT, patients with MB disease are clearly at risk of relapse. In our opinion, there's still a need to identify those at risk, to improve infrastructures for long-term follow-up and also to develop effective and more appealing therapies for MB Hansen's disease.…”

Section: Discussionmentioning

confidence: 99%

Hansen's disease in Portugal: multibacillary patients treated between 1988 and 2003

Medeiros

Catorze²,

Vieira

2009

Journal of the European Academy of Dermatology and Venereology

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A Second Case of Multidrug-resistant Mycobacterium leprae Isolated from a Japanese Patient with Relapsed Lepromatous Leprosy

Cited by 38 publications

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Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

¿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

Hansen's disease in Portugal: multibacillary patients treated between 1988 and 2003

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