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1.
Am J Case Rep ; 25: e942048, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351602

RESUMO

BACKGROUND Leprosy, also known as Hansen's disease, is a neglected tropical disease with low prevalence in the United States. The disease's long incubation period can cause delayed presentation, and most affected individuals have a history of travel or work in leprosy-endemic regions. The immune response to Mycobacterium leprae determines the clinical characteristics of leprosy, with tuberculoid leprosy being characterized by well-defined granulomas and involvement of peripheral nerves. The recommended treatment is a combination of dapsone and rifampin for 12 months. CASE REPORT A 78-year-old man with a history of extensive travel to Africa and Asia 50 years ago, presented with a non-tender, non-pruritic, and hypopigmented skin lesion on his left knee. Biopsy results confirmed granulomatous inflammation and the presence of Mycobacterium leprae, leading to a diagnosis of tuberculoid/paucibacillary leprosy. The patient received dapsone and rifampin treatment, which resulted in symptom improvement. CONCLUSIONS The patient's long incubation period of 50 years between exposure and symptom onset is remarkable and possibly one of the longest reported for tuberculoid leprosy. It emphasizes the importance of considering leprosy in cases with an extensive travel history and long incubation periods. Our patient's case presented contradictory staining results, suggesting potential sampling variation or a rare mixed leprosy form. Based on his clinical findings, he was diagnosed with tuberculoid leprosy. Early diagnosis and treatment are crucial to prevent irreversible nerve damage and improve patient outcomes. Healthcare providers should be vigilant in acquiring a detailed travel history to facilitate early diagnosis and appropriate management of leprosy cases.


Assuntos
Hanseníase Tuberculoide , Hanseníase , Masculino , Humanos , Idoso , Hanseníase Tuberculoide/diagnóstico , Hanseníase Tuberculoide/tratamento farmacológico , Hanseníase Tuberculoide/patologia , Rifampina/uso terapêutico , Período de Incubação de Doenças Infecciosas , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/patologia , Mycobacterium leprae , Dapsona/uso terapêutico
2.
Am J Trop Med Hyg ; 109(6): 1260-1265, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37931307

RESUMO

Since the introduction of multidrug therapy (MDT), various disabilities/morbidities due to leprosy have been prevented. However, there is a subset of patients in whom the skin lesions do not resolve completely or remain unchanged despite a full course of MDT, which is a great source of anxiety to the patient and their family members. Hence, we tried to ascertain the putative causes and risk factors of persistent skin lesions (PSLs) by analyzing the clinical, histopathological, bacteriological, and drug resistance patterns. This is a retrospective, cohort study wherein 35 patients who had PSLs after completion of MDT were included. The majority of the patients were 18 to 30 years of age, with males predominating. Borderline tuberculoid leprosy was the most common clinical spectrum observed (71.4%). The majority had PSLs distributed predominantly over photo-exposed sites (upper limbs > trunk > face). Eight patients (22.8%) had a history of contact with leprosy patients in their family, and six patients (17.1%) had associated comorbidities. Improvement in histopathological parameters such as a decrease in granuloma fraction was observed in 22 patients (62.8%) with PSLs after release from treatment in comparison with baseline. Four patients (11.4%) were noted to have drug resistance (three to rifampicin and one to dapsone). Thus, our study emphasizes that leprosy patients with PSLs after completion of MDT should undergo histopathological evaluation and drug resistance studies.


Assuntos
Hanseníase , Dermatopatias , Masculino , Humanos , Hansenostáticos , Estudos Retrospectivos , Quimioterapia Combinada , Estudos de Coortes , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/uso terapêutico , Dapsona/efeitos adversos , Dermatopatias/tratamento farmacológico
3.
J Glob Antimicrob Resist ; 35: 262-267, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37852372

RESUMO

OBJECTIVES: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. METHODS: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. RESULTS: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. CONCLUSIONS: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Ofloxacino/farmacologia , Quimioterapia Combinada , Estudos Transversais , Farmacorresistência Bacteriana/genética , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/farmacologia , Dapsona/uso terapêutico , Índia/epidemiologia
4.
Naunyn Schmiedebergs Arch Pharmacol ; 396(7): 1501-1511, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36773052

RESUMO

Viral respiratory diseases (VRDs) cause lung inflammation and inflammatory cytokine production. We study whether dapsone is responsible for its observed preventive treatment effects of the sustained viral RNA interferon response. Around 2008 and 2012, Korea's Dementia Management Act stipulated drastic changes in the administration of dementia medication by medical staff. Participants were randomized and we compared leprosy patients with VRDs after prescribing dapsone as a standard treatment from 2005 to 2019. Significance was evaluated based on the dapsone-prescribed (+) subgroup and the dapsone-unprescribed (-) subgroup of the VRD diagnosed (+) and VRD undiagnosed (-) subgroup. We analyzed VRD ( +)/(- with dapsone (+)/(-) group and used a T-test, and designed the equation of acetylation with dapsone and acetylcholine (AA) equation. The 6394 VRD participants who received the dapsone intervention compared to the 3255 VRD participants in the control group demonstrated at T2 VRD (+) dapsone (-) (mean (M) = 224.80, SD = 97.50): T3 VRD (-) dapsone (+) (M = 110.87, SD = 103.80), proving that VRD is low when dapsone is taken and high when it is not taken. The t value is 3.10, and the p value is 0.004395 (significant at p < 0.05). After an increase in VRDs peaked in 2009, bronchitis, COPD, and pneumonia surged in 2013. The AA equation was strongly negatively correlated with the prevalence of bronchitis and chronic obstructive pulmonary disease (COPD): with bronchitis, r(15) = -0.823189, p = 0.005519, and with COPD, r(15) = -0.8161, p = 0.000207 (significant at p < 0.05). Dapsone treated both bronchitis and COPD. This study provides theoretical clinical data to limit acetylcholine excess during the VRD pandemic for bronchitis, COPD, and pneumonia.


Assuntos
Bronquite , Demência , Hanseníase , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Acetilcolina , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Bronquite/tratamento farmacológico , Dapsona/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia
6.
Int J Mol Sci ; 23(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36293307

RESUMO

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.


Assuntos
Hanseníase , Rifampina , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Dapsona/farmacologia , Dapsona/uso terapêutico , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Ofloxacino/uso terapêutico , Farmacorresistência Bacteriana/genética , Mycobacterium leprae/genética , Hanseníase/tratamento farmacológico , Hanseníase/genética , Mutação , Aminoácidos/genética , Testes de Sensibilidade Microbiana
7.
Naunyn Schmiedebergs Arch Pharmacol ; 395(12): 1509-1523, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36125533

RESUMO

The 4,4'-diaminodiphenyl sulfone (DDS), also known as dapsone, is traditionally used as a potent anti-bacterial agent in clinical management of leprosy. For decades, dapsone has been among the first-line medications used in multidrug treatment of leprosy recommended by the World Health Organization (WHO). Shortly after dapsone's discovery as an antibiotic in 1937, the dual function of dapsone (anti-microbial and anti-inflammatory) was elucidated. Dapsone exerts its anti-bacterial effects by inhibiting dihydrofolic acid synthesis, leading to inhibition of bacterial growth, while its anti-inflammatory properties are triggered by inhibiting reactive oxygen species (ROS) production, reducing the effect of eosinophil peroxidase on mast cells and downregulating neutrophil-mediated inflammatory responses. Among the leading mechanisms associated with its anti-microbial/anti-protozoal effects, dapsone clearly has multiple antioxidant, anti-inflammatory, and anti-apoptotic functions. In this regard, it has been described in treating a wide variety of inflammatory and infectious skin conditions. Previous reports have explored different molecular targets for dapsone and provided insight into the anti-inflammatory mechanism of dapsone. This article reviews several basic, experimental, and clinical approaches on anti-inflammatory effect of dapsone.


Assuntos
Dapsona , Hanseníase , Humanos , Dapsona/farmacologia , Dapsona/uso terapêutico , Hanseníase/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Espécies Reativas de Oxigênio
8.
J Glob Antimicrob Resist ; 30: 282-285, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35717020

RESUMO

OBJECTIVES: Purulia is one of the high-endemic districts for leprosy in West Bengal (the eastern part of India). The annual new case detection rate (ANCDR) of leprosy in West Bengal is 6.04/100000 (DGHS 2019-20). Our earlier report provided evidence of secondary drug resistance in relapse cases of leprosy. The aim of the current study was to observe primary drug resistance patterns for dapsone, rifampicin, and ofloxacin amongst new leprosy patients from Purulia, West Bengal in order to better understand the emergence of primary resistance to these drugs. METHODS: In the present study, slit-skin smear samples were collected from 145 newly diagnosed leprosy cases from The Leprosy Mission (TLM) Purulia hospital between 2017 and 2018. DNA was extracted from these samples and the Mycobacterium leprae genome was analyzed for genes associated with drug resistance by polymerase chain reaction (PCR), followed by Sanger sequencing. Wild-type strain (Thai-53) and mouse footpad-derived drug-resistant strain (Z-4) were used as reference strains. RESULTS: Of 145 cases, 25 cases showed mutations in genes associated with resistance to rifampicin, dapsone, and ofloxacin (as described by the World Health Organization, rpoB, folP, and gyrA, respectively) through Sanger sequencing. Of these 25 cases, 16 cases showed mutations in ofloxacin, two cases showed mutations in combinations of ofloxacin and rifampicin, four cases showed a mutation only in rifampicin, one case showed mutations in combinations of rifampicin and dapsone, and two cases showed mutations only in dapsone. CONCLUSION: Results from this study indicated the emergence of resistance to antileprosy drugs in new cases of leprosy. As ofloxacin is the alternate drug for the treatment of rifampicin-resistant cases, the emergence of new cases with resistance to ofloxacin indicates that ofloxacin-resistant M. leprae strains are actively circulating in this endemic region (i.e., Purulia, West Bengal), posing challenges for the effective treatment of rifampicin-resistant cases.


Assuntos
Hanseníase , Rifampina , Animais , Dapsona/farmacologia , Dapsona/uso terapêutico , Farmacorresistência Bacteriana/genética , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase/microbiologia , Camundongos , Mycobacterium leprae/genética , Ofloxacino/farmacologia , Ofloxacino/uso terapêutico , Rifampina/farmacologia , Rifampina/uso terapêutico
9.
J Glob Antimicrob Resist ; 30: 459-467, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35643395

RESUMO

OBJECTIVES: Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn assisting in implementing better control strategies for leprosy elimination. METHODS: A systematic literature search was conducted in PubMed, Embase, Medline, and Web of Science. Two independent reviewers selected the literature according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), extracted data, and evaluated the risk of bias. Drug resistance data were pooled using the random-effects model. Subgroup analysis was performed based on across sampling time, region, study population (treatment status, relapses status), and sample size. RESULTS: A total of 30 studies were included. The results of meta-analysis showed that the dapsone resistance rate of leprosy patients after treatment was 8% (95% confidence interval [CI], 6%-10%). Compared to the rates of primary resistance of new cases without treatment therapy (pooled incidence, 4% [95% CI, 2%-5%]), treatment cases (13% [95% CI 9%-16%]) had secondary resistance, and relapse cases (26% [95% CI, 18%-33%]) had drug resistance. In addition, the drug resistance rate of monotherapy was significantly increased than that of relapsed patients treated with diamino-diphenylsulfone monotherapy. Subgroup analysis showed that the patients in the Western Pacific have the highest dapsone resistance, and the resistance to dapsone was slightly lower after 2005. For sample size, the rate in the group under 100 samples was significantly higher than in the other. CONCLUSION: Dapsone resistance is closely related to leprosy relapse and long-term drug use. Dapsone monotherapy is one of important reasons for drug resistance in relapsed cases. Drug resistance varies among different populations and regions of the world.


Assuntos
Dapsona , Hanseníase , Dapsona/farmacologia , Dapsona/uso terapêutico , Humanos , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Mycobacterium leprae , Recidiva , Fatores de Risco
10.
Antimicrob Agents Chemother ; 66(5): e0217021, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35435708

RESUMO

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (folP1), rifampin (rpoB), and ofloxacin resistance (gyrA) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relationship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group.


Assuntos
Hansenostáticos , Hanseníase , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil/epidemiologia , Estudos Transversais , Dapsona/uso terapêutico , Farmacorresistência Bacteriana/genética , Quimioterapia Combinada , Humanos , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase/microbiologia , Testes de Sensibilidade Microbiana , Mycobacterium leprae/genética , Recidiva , Rifampina/farmacologia , Rifampina/uso terapêutico
11.
Curr Top Med Chem ; 22(19): 1611-1625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34503409

RESUMO

BACKGROUND: Leprosy (Hansen's disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while "reemergence" is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. OBJECTIVES: The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts. METHODS: Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1. RESULTS: Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. CONCLUSION: A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.


Assuntos
Hansenostáticos , Hanseníase , Efeitos Psicossociais da Doença , Dapsona/farmacologia , Dapsona/uso terapêutico , Quimioterapia Combinada , Humanos , Hansenostáticos/química , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Simulação de Acoplamento Molecular , Mycobacterium leprae , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
12.
Indian J Dermatol Venereol Leprol ; 88(2): 137-143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34623042

RESUMO

Psoriasis is a common skin disease that affects 1-3% of the general population. The treatment depends on body surface area involved, quality of life impairment and associated comorbidities. The treatment options include topical therapy, phototherapy, conventional systemic therapy (methotrexate, cyclosporine and acitretin), biologics and oral small molecules (apremilast and tofacitinib). Despite the availability of newer therapies such as biologics and oral small molecules, many a time, there is a paucity of treatment options due to the chronic nature of the disease, end-organ toxicity of the conventional drugs or high cost of newer drugs. In these scenarios, unconventional treatment options may be utilized as stand-alone or adjuvant therapy. In this review, we have discussed these uncommonly used treatment options in the management of psoriasis.


Assuntos
Psoríase/terapia , Antibacterianos/uso terapêutico , Cirurgia Bariátrica , Bevacizumab/uso terapêutico , Colchicina/uso terapêutico , Dapsona/uso terapêutico , Dieta , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Fumaratos/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Fatores Imunológicos/uso terapêutico , Isotretinoína/uso terapêutico , Estilo de Vida , Probióticos/uso terapêutico , Somatostatina/uso terapêutico , Sulfassalazina/uso terapêutico , Tiazolidinedionas/uso terapêutico
13.
Indian J Dermatol Venereol Leprol ; 88(4): 519-522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33871212

RESUMO

Background Dapsone treatment may reduce HbA1c levels in patients with diabetes. Aims To assess the prevalence and characteristics of dapsone associated reduction of HbA1c in patients with Hansen's disease. Methods A retrospective data review of outpatient and inpatient charts of consecutive patients with Hansen's disease and type 2 diabetes mellitus was conducted over two years from January 2014 to January 2016 at the Department of Dermatology, CMC Vellore, India. Results Of the 245 patients with a confirmed diagnosis of Hansen's disease who were on oral dapsone 100 mg/day as part of their treatment regimen, 49 patients had diabetes and were eligible for the study as per predetermined inclusion criteria. Of these, 35 subjects (71%) had an HbA1c discordantly lower than the corresponding mean plasma glucose levels. Patients with discordant HbA1c levels were more likely to be male and to have a higher RBC mean corpuscular volume (MCV). A greater reduction in HbA1c levels was seen during the initial 3 months of therapy of dapsone treatment. Limitations The small sample size and retrospective design were limitations of this study. Also, we did not analyze the role of methemoglobinemia or the utility of alternative measures of glycemic control in these patients. Conclusion We describe a high prevalence of dapsone associated inappropriate HbA1c lowering in type 2 diabetes mellitus patients. This may have serious implications for the management of diabetes in patients on therapy with dapsone.


Assuntos
Diabetes Mellitus Tipo 2 , Hanseníase , Dapsona/uso terapêutico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobinas Glicadas , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Masculino , Estudos Retrospectivos
14.
Washington; s.n; 2022. 9 p. tab, mapa.
Não convencional em Inglês | SES-SP, HANSEN, HANSENIASE, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1402124

RESUMO

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (folP1), rifampin (rpoB), and ofloxacin resistance (gyrA) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relation ship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group


Assuntos
Humanos , Rifampina , Brasil/epidemiologia , Testes de Sensibilidade Microbiana , Estudos Transversais , Farmacorresistência Bacteriana/genética , Dapsona/uso terapêutico , Quimioterapia Combinada , Hansenostáticos , Hanseníase , Hanseníase/microbiologia , Hanseníase/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia
17.
PLoS Negl Trop Dis ; 15(7): e0009635, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34319982

RESUMO

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.


Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Corticosteroides/uso terapêutico , Vacina BCG/administração & dosagem , Brasil/epidemiologia , COVID-19/diagnóstico , Teste para COVID-19 , Clofazimina/uso terapêutico , Estudos de Coortes , Dapsona/uso terapêutico , Humanos , Pentoxifilina/uso terapêutico , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Análise de Sobrevida , Talidomida/uso terapêutico , Tratamento Farmacológico da COVID-19
18.
PLoS Negl Trop Dis ; 15(5): e0009382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33939710

RESUMO

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Pele/microbiologia , Pele/patologia , Adulto Jovem
20.
Ocul Immunol Inflamm ; 29(6): 1121-1125, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32159415

RESUMO

Purpose: To describe a case of leprosy presenting chronic anterior uveitis associated with other systemic lesions.Methods: Case report and systematic literature review.Results: We describe the case of a 65-year-old patient presenting clinical features of chronic uveitis and poor response to topical and intravitreal steroid treatment. Upon ocular examination, diffuse iris atrophy and macular edema were observed and laboratory tests for autoimmune and infectious diseases were within normal range. Physical examination revealed the presence of skin lesions on trunk and extremities, which were biopsied and identified as positive for leprosy.Conclusion: The case reported herein presented atypical characteristics of uveitis due to the involvement of the posterior segment of the eye. Leprosy diagnosis could be a challenge, a systematic approach is mandatory to achieve adequate treatment.


Assuntos
Infecções Oculares Bacterianas/diagnóstico , Hanseníase Virchowiana/diagnóstico , Mycobacterium leprae/isolamento & purificação , Uveíte Anterior/diagnóstico , Idoso , Atrofia , Biópsia , Doença Crônica , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Quimioterapia Combinada , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Humanos , Iris/patologia , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/microbiologia , Edema Macular/diagnóstico por imagem , Masculino , Rifampina/uso terapêutico , Pele/microbiologia , Pele/patologia , Tomografia de Coerência Óptica , Uveíte Anterior/tratamento farmacológico , Uveíte Anterior/microbiologia
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