Emergence of primary drug resistance to rifampicin in Mycobacterium leprae strains from leprosy patients in India

Lavania, Mallika; Nigam, A. N.; Turankar, Ravindra P.; Singh, Itu; Gupta, Prosenjit; Kumar, Sandip; Sengupta, Utpal; John, Annamma

doi:10.1016/j.cmi.2015.08.004

Cited by 23 publications

(15 citation statements)

References 4 publications

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“…Finally, none of these studies reported antibiotic resistance pattern of M. leprae. There are reports on drug resistance in leprosy patients [45][46][47][48][49] and can be one of the reasons of the relapse rate increase in the last years [50]. Considering some of the areas with leprosy had also high incidence of resistant tuberculosis (such us India) and MDT share rifampin as an important drug with sensitive tuberculosis, closer follow-up and drug resistance studies should be done in these areas.…”

Section: Limitations and Strengthsmentioning

confidence: 99%

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis

et al. 2020

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Background: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. Methods: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). Results: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. Conclusion: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

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Section: Limitations and Strengthsmentioning

confidence: 99%

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis

et al. 2020

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“…1), are characteristic molecular signatures of DDS-resistance 2,11,12 . Recently, rifampicin was reported to be ineffective against Ml 13,14 . Thus, there is a look for an additional alternative potent agent(s) against leprosy in a relatively short time, as DDS-resistant bacilli spread fast.…”

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confidence: 99%

Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae

Swain

Paidesetty

Dehury

et al. 2020

Sci Rep

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Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with treatment by the on-going multidrug therapy (MDT). Today, dapsone (DDS) resistance has led to fear of leprosy in more unfortunate people of certain developing countries. Herein, DDS was chemically conjugated with five phytochemicals independently as dapsone-phytochemical conjugates (DPCs) based on azo-coupling reaction. Possible biological activities were verified with computational chemistry and quantum mechanics by molecular dynamics simulation program before chemical synthesis and spectral characterizations viz., proton-HNMR, FTIR, UV and LC-MS. The in vivo antileprosy activity was monitored using the 'mouse-foot-pad propagation method', with WHO recommended concentration 0.01% mg/kg each DPC for 12 weeks, and the host-toxicity testing of the active DPC4 was seen in cultured-human-lymphocytes in vitro. One-log bacilli cells in DDS-resistant infected mice footpads decreased by the DPC4, and no bacilli were found in the DDS-sensitive mice hind pads. Additionally, the in vitro host toxicity study also confirmed that the DCP4 up to 5,000 mg/L level was safety for oral administration, since a minor number of dead cells were found in red color under a fluorescent microscope. Several advanced bioinformatics tools could help locate the potential chemical entity, thereby reducing the time and resources required for in vitro and in vitro tests. DPC4 could be used in place of DDS in MDT, evidenced from in vivo antileprosy activity and in vitro host toxicity study.

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“…Although reports of emerging drug resistance in Mycobacterium leprae have emerged from various parts of the world, including India, data on the clinico-epidemiological features and management of this subset of patients are lacking. [3][4][5][6] We have faced similar state of affairs over the past few years in the leprosy unit of our tertiary care center and, therefore, attempted to perform a retrospective analysis of such "nonresponsive" MB cases. Herein, we attempt to share our experience regarding the effectiveness and safety of alternate anti-leprosy treatment (ALT) comprising minocycline, ofloxacin, and clofazimine in treating WHO-MDT-MBR refractory leprosy patients, in the absence of facilities for resistance studies.…”

Section: Introductionmentioning

confidence: 99%

Alternate Anti-Leprosy Regimen for Multidrug Therapy Refractory Leprosy: A Retrospective Study from a Tertiary Care Center in North India

Narang

Bishnoi

Dogra

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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A subset of multibacillary (MB) leprosy patients manifest with clinical "nonresponsiveness" to the fixedduration, World Health Organization multidrug therapy MB regimen (WHO-MDT-MBR). The aim of this retrospective study was to assess the effectiveness and safety of alternate anti-leprosy therapy (ALT) in such patients. This is an analysis of patients' records, registered in the leprosy clinic of our institute over a period of 6 years (2010-2015). The criteria for inadequate response/nonresponsiveness to treatment were as follows: 1) persistent/new lesions after completing ³ 12 months of WHO-MDT-MBR (isolated reactions were ruled out histopathologically) and 2) persistent positive/ increasing value of the morphological index (MI) and a 2 log increase in the bacteriological index (BI) after ³ 12 months of WHO-MDT-MBR. Such cases were treated with ALT consisting of minocycline, clofazimine, and ofloxacin (24 months). Of 556 patients registered during the study period, 40.3% (224) were slit-skin smear (SSS) positive and 59.7% (332) were SSS negative. Of all, 35 patients (6.3%) satisfied the criteria for clinical nonresponsiveness. Of 224 SSS-positive patients, these 35 patients amounted to 15.6%. The mean BI and MI of these patients after completion of ³ 12 months of WHO-MDT-MBR were 5.3 ± 0.6 and 14 ± 6.8%, respectively. After 6 months of treatment with ALT, MI became negative (0) in all these patients. After completion of ALT, the mean BI and MI became 1.7 ± 0.7 and 0%, respectively (P < 0.0001). There were 16 patients with corticosteroid-dependent recurrent/chronic erythema nodosum leprosum, who had excellent response with significant reduction in the number of reactional episodes and mean dose of prednisolone required (P < 0.0001). No serious adverse effects were noted. We conclude that ALT is safe and effective in the management of MB leprosy patients who are nonresponsive to 12 months of WHO-MDT-MBR.

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Emergence of primary drug resistance to rifampicin in Mycobacterium leprae strains from leprosy patients in India

Cited by 23 publications

References 4 publications

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis

Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae

Alternate Anti-Leprosy Regimen for Multidrug Therapy Refractory Leprosy: A Retrospective Study from a Tertiary Care Center in North India

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