Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?

Chaves, Luíse L.; Patriota, Yuri Basílio Gomes; Sobrinho, José Lamartine Soares; Vieira, Alexandre C.C.; Lima, Sofia A. Costa; Reis, Salette

doi:10.3390/pharmaceutics12121202

Cited by 10 publications

(5 citation statements)

References 99 publications

(116 reference statements)

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“…Despite the many efforts to eradicate this disease, concerns over concomitants, such as poverty, delayed diagnosis, and drug resistance, have emerged. 2 , 39 , 40 The PGL-1 molecule has significantly contributed to the serodiagnosis of Hansen’s disease, providing a specific target to identify M. leprae . 10 Currently, the PGL-1-based ELISA test still contributes to determining whether a patient is free from leprosy bacilli.…”

Section: Discussionmentioning

confidence: 99%

“…The strategy of controlling leprosy still must be reinforced with new diagnostic tools in combination with improved therapeutic regimens. 2 Moreover, the risk of drug resistance remains a latent threat; thus, cautious surveillance is necessary for preventing the spread of drug-resistant strains. 3 Innovative therapies have been proposed as strategies to combat infection and antibiotic resistance by targeting pivotal bacterial processes, such as adhesion, cell wall permeability, quorum sensing, virulence regulons, and toxin production.…”

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confidence: 99%

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Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry

Arenas

Pieffet

Rocha-Roa

et al. 2022

Mem. Inst. Oswaldo Cruz

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BACKGROUND Mycobacterium leprae, the causative agent of Hansen's disease, causes neural damage through the specific interaction between the external phenolic glycolipid-1 (PGL-1) and laminin subunit alpha-2 (LAMA2) from Schwann cells.OBJECTIVE To design a LAMA2-based peptide that targets PGL-1 from M. leprae.METHODS We retrieved the protein sequence of human LAMA2 and designed a specific peptide using the Antimicrobial Peptide Database and physicochemical parameters for antimycobacterial peptide-lipid interactions. We used the AlphaFold2 server to predict its three-dimensional structure, AUTODOCK-VINA for docking, and GROMACS programs for molecular dynamics simulations.FINDINGS We analysed 52 candidate peptides from LAMA2, and subsequent screening resulted in a single 60-mer peptide. The mapped peptide comprises four β-sheets and a random coiled region. This peptide exhibits a 45% hydrophobic ratio, in which one-third covers the same surface. Molecular dynamics simulations show that our predicted peptide is stable in aqueous solution and remains stable upon interaction with PGL-1 binding. In addition, we found that PGL-1 has a preference for one of the two faces of the predicted peptide, which could act as the preferential binding site of PGL-1.MAIN CONCLUSIONS Our LAMA2-based peptide targeting PGL-1 might have the potential to specifically block this key molecule, suggesting that the preferential region of the peptide is involved in the initial contact during the attachment of leprosy bacilli to Schwann cells.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry

Arenas

Pieffet

Rocha-Roa

et al. 2022

Mem. Inst. Oswaldo Cruz

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“…Patients with MB and PB can be treated with MDT for 12 and 6 months, respectively. Drug resistance has been reported since 1964 and has gradually increased despite MDT [4]. Drug resistance and relapse remain major public health issues in the control of leprosy.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis and Treatment of Leprosy in Taiwan during the COVID-19 Pandemic: A Retrospective Study in a Tertiaty Center

Hsieh,

Hsiao

2023

Diagnostics

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Currently, over 200,000 new cases of leprosy are reported annually worldwide. Although leprosy was thought to have been eradicated in Taiwan, a few new cases still occur annually. Protean clinical manifestations of leprosy and immunological reactions result in delayed diagnoses. In addition, drug-resistant leprosy is emerging and poses treatment challenges. In this retrospective study, we collected and analyzed the clinicopathological features, leprosy type, treatment response, and relapse rate of patients with leprosy in our hospital between January 2009 and November 2022. We found that 54% of patients were Indonesian, and borderline lepromatous leprosy was predominant (39%); moreover, histoid leprosy and the Lucio phenomenon were also reported. Polymerase chain reaction analysis identified four positive cases, including a dapsone-resistant (4%) case. Our findings indicated good control of leprosy and a lower rate of dapsone resistance than that reported by the World Health Organization (4% vs. 13%) from 2009 to 2015. We found that the patient profile in terms of the treatment duration, recurrence rate, systemic symptoms, and neurological symptoms did not differ between before and during the pandemic. We report the recent advances in leprosy diagnosis, drug-resistant gene mutations, post-exposure prophylaxis, vaccination, and the effect of coronavirus disease 2019 on leprosy to facilitate updated leprosy diagnosis and management.

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“…Since 1940, dapsone (DDS) has been considered the most effective antibacterial and anti-inflammatory drug against Mycobacterium leprae . Nevertheless, the first DDS-resistant strain of Mycobacterium leprae was discovered in 1964 [ 4 ]. In 1981, WHO introduced multidrug therapy (MDT) for leprosy as a priority strategy to reduce drug resistance: the first-line drugs (rifampicin, ampicillin, and clofazimine) and second-line drugs (minocycline, ofloxacin, and clarithromycin).…”

Section: Introductionmentioning

confidence: 99%

Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis

Li,

Yang

et al. 2022

IJMS

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Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85–12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46–15.33) vs. 6.59% (3.66–9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65–9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82–18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02–5.77), 3.66% (95% CI: 2.41–4.90) and 1.28% (95% CI: 0.87–1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83–2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.

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Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?

Cited by 10 publications

References 99 publications

Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry

Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry

Diagnosis and Treatment of Leprosy in Taiwan during the COVID-19 Pandemic: A Retrospective Study in a Tertiaty Center

Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis

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