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

Prasad, P. V. S.; Kaviarasan, P K

doi:10.4103/0019-5154.74528

Cited by 40 publications

(28 citation statements)

References 28 publications

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“…One MDR relapse case, however, showed such a short incubation period (1 month) that we suspect that this patient had not really been cured from his second disease course (Table 3). Our observation that all resistant cases were males is in agreement with findings of other studies (29,30) and could be associated with the higher prevalence of males in MB leprosy and more frequent irregular self-administered drug intake (including quinolones) in males, causing mainly secondary resistance. This is supported by the recent observation of Singh et al (34) showing the absence of primary drug resistance as demonstrated by the lack of drug-related mutations in strains from new leprosy patients.…”

Section: Discussionsupporting

confidence: 82%

“…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).…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 82%

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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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“…Gupta et al (25) found that this fairly arbitrary model based on the number of lesions that are identifiable can result in both over-and underdiagnosis of HD; they suggested adding additional criteria that take into account the size of the lesions and accompanying nerve enlargement. Prasad and Kaviarisan (26) note that the WHO classification system contains no treatment protocol for cases of neuritic HD in which no skin lesions or changes are present. A more nuanced system of classification recognizes a spectrum of cell-mediated responses to the disease, with five categories of the disease (23,24); these include, from the least to the most severe (or the greatest to the least immune response), tuberculoid (TT) (Fig.…”

Section: The Hd Bacillus and Its Impactmentioning

confidence: 99%

Leprosy in the 21st Century

2015

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SUMMARY Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as “leprosy reactions,” which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.

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“…The WHO project for Global Surveillance of Drug Resistance came at a most opportune time in 2008 in light of the wide disparity among countries and even among different regions within the same country regarding investigative approaches, management and collection of relapse data and patient samples [59]. At present, little information can be obtained from the vast majority of endemic countries, clearly indicative of relapse under reporting and weak monitoring capacity of the project [60].…”

Section: ■ Resistancementioning

confidence: 99%

“…In addition, current treatment is exceedingly long and reports of resistance against some of its component antibiotics are increasingly frequent. The general consensus is that new drugs are needed to develop a shorter, single treatment scheme [9][10][11][12]. A short scheme will certainly improve patient adherence and their quality of life.…”

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confidence: 99%

Considerations on clinical trials of leprosy treatment: need of novel drug combinations

Illarramendi¹,

Oliveira²,

Sales³

et al. 2013

Clinical Investigation

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Considering that after 30 years of using multidrug therapy (MDT), leprosy eradication has still not been achieved, leprosy treatment must remain on the drug discovery agenda. Due to the complexities inherent in leprosy disease and the many methodological issues involved in clinical trials, the task of translating the bench findings into clinical practice has been arduous. While the effectiveness of reducing the currently recommended MDT remains controversial, a number of highly bactericidal antibiotics and immune-modulatory drugs have emerged as prospective candidates to improve patient adherence and quality of life, reduce adverse effects and prevent resistance. To replace the standard WHO-MDT, the new combination must be the shortest, simplest and, consequently, most affordable treatment possible.

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

Cited by 40 publications

References 28 publications

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

Leprosy in the 21st Century

Considerations on clinical trials of leprosy treatment: need of novel drug combinations

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