BORDERLINE TUBERCULOID LEPROSY: CLINICOPATHOLOGICAL EVALUATION OF MULTIDRUG THERAPY.
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ABSTRACT:
SUBMITTER: Kar PK
PROVIDER: S-EPMC5530813 | biostudies-other | 1997 Apr
REPOSITORIES: biostudies-other
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Project description:Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.
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Project description:This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.
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Project description:Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.
2007-12-12 | E-GEOD-443 | biostudies-arrayexpress
Project description:Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective.
| S-EPMC7866323 | biostudies-literature
Project description:ObjectivesNeuropathic pain (NP) can occur as a chronic complication of leprosy neuropathy. NP epidemiology and its impact on patients have not been well documented. This study investigates NP prevalence and impact in the years after patients are declared "released from treatment" (RFT) following multidrug therapy (MDT) completion.MethodsIn this cross-sectional study, 85 RFT patients were recruited within leprosy referral services in Nepal. The Douleur Neuropathique 4 Questionnaire (DN4) was used to screen for NP. Pain severity, impacts on patients' daily activities and mental health were measured by using the Brief Pain Inventory (BPI), Screening of Activity Limitation and Safety Awareness (SALSA), and General Health Questionnaire-12 (GHQ-12) respectively.Results96% surveyed had been treated for multibacillary leprosy. 44 (52%) complained of pain of which 30 (68%) were diagnosed with NP. NP was not associated with age, gender, or presence of skin lesions or nerve symptoms at leprosy diagnosis. 70% of patients with NP had either history of or ongoing reactions and 47% had grade 2 disability. Nerve tenderness (p = 0.023) and current reactions (p = 0.018) were significant risk factors for NP. Patients with NP suffered significantly higher intensity pain (p = 0.023) and daily life interference (p = 0.003) and were more likely to have moderate to extreme daily activity limitations (p = 0.005). 13 (43%) exhibited psychological distress, and medications only reduced moderate degree (50-60%) of pain.ConclusionsIn our study, 35% of RFT patients had ongoing NP. Risk factors include nerve tenderness and reaction. They suffer from more daily life interference and psychological distress. Leprosy patient care should include recognition and management of NP.
| S-EPMC6044550 | biostudies-literature
Project description:Sequences of the folP1, rpoB, and gyrA genes were analyzed for 88 isolates of Mycobacterium leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines. Thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant M. leprae.
| S-EPMC90887 | biostudies-literature
Project description:BACKGROUND:Leprosy continues to be a public health problem in many countries. Difficulties faced by health services include late diagnosis, under-reporting of new cases, adequate monitoring of disabilities and treatment. Furthermore, systematic follow-up after completion of treatment is important, when new disabilities may occur, or existing disabilities may get worse. The objective of the present study was to determine the prevalence of leprosy-associated grade 2 disabilities (G2D) after completion of multidrug therapy (MDT) and to identify factors associated with G2D. METHODS:We performed a cross-sectional study of 222 leprosy cases registered in Vitória da Conquista, Bahia state, Brazil from 2001-2014. We performed a clinical examination of the study participants and collected socio-economic and clinical information by interview. We identified factors associated with grade 2 disability (G2D) using logis tic regression. RESULTS:In total, 38 (17.1%) participants were diagnosed with G2D, and 106 (47.7%) with grade 1 disabilities (G1D). The following independent factors were significantly associated with G2D: occurrence of leprosy reaction (adjusted OR = 2.5; 95%CI = 1.09-5.77), thickening and/or tenderness of one or more nerve trunks (adjusted OR = 3.0; CI = 1.13-8.01) and unemployment (adjusted OR = 7.17; CI = 2.44-21.07). CONCLUSIONS:This study shows that physical disabilities remain after completion of MDT and frequently occur in an endemic area in Brazil. Finding new ways to reduce the burden of disability are urgently needed, and may include systematic follow-up of patients after treatment completion combined with evidence-based preventative measures.
| S-EPMC6062121 | biostudies-literature
Project description:If leprosy is a public health problem, it is due to the disabilities it causes. Surprisingly little is known about the risk of disabilities. Even now, mainly cross-sectional studies report disability prevalence. The present study aims to report the risk of disability in pre and post-WHO multidrug therapy (MDT) in multibacillary leprosy patients and to assess the extent of the incidence of disability.The study design is prospective and the setting is an institutional field area. Patients were detected during 2001-6 field surveys. Of the 289 multibacillary patients, 146 completed the study. Both sexes were involved. The primary outcome planned was to study cure of disease, relapses and disability in patients receiving MDT. The secondary outcome was to measure reaction and default. Assessment was done clinically. Data have been analysed using SPSS software, logistic, survival analysis was performed and the ?(2) test of significance was used.An important risk factor was found to be three or more nerves involved with odds of 3.73 (1.24-11.2), and delay in treatment; 2.27 (1.04-4.96) at the pre-MDT stage and three or more nerves involved with odds of 2.81 (1.0-7.9) at the post-MDT stage. The incidence of disability was found to be 2.74/100 person-years; 2.69 in the MDT arm and 2.84 in defaulters, with slightly higher disability among early defaulters (3.08) than among late defaulters (2.30). The study suggests that the incidence of disability could be slightly higher if treatment is not completed.Early treatment for leprosy is a must for reducing the risk of disability, and treatment delay would increase the risk of disability. It is important to note that the incidence of disability between defaulters and those completing treatment was not found to be significantly different.
| S-EPMC3330256 | biostudies-other
Project description:BACKGROUND:Type 1 leprosy reaction, also known as "reversal reaction", is related to cellular immune responses to Mycobacterium leprae antigens. The risk factors that trigger type 1 leprosy reactions are poorly understood. Leprosy with concurrent tetanus is rare, and there are no publicly available reports of a leprosy patient infected with tetanus that induced type 1 leprosy reactions. CASE PRESENTATION:A 56-year-old Chinese Han female presented to our hospital with symptoms of erythematous plaques and pain over her left upper limb for 2 days and foreign object sensation in her throat for 3 days. The patient had a 6-year history of leprosy. Type 1 leprosy reactions were initially considered, followed by treatment with methylprednisolone. Two days later, the patient's symptoms were aggravated, with neck muscle tension and difficulty in opening her mouth, and the erythematous plaques had spread over most of her left upper limb. After further careful examinations, we confirmed the diagnosis of tetanus with concurrent type 1 leprosy reactions. The patient was given anti-tetanus treatment for 12 days and anti-leprosy reaction treatment for 4 months; the diseases were eventually controlled. CONCLUSIONS:This report suggests that tetanus infection may be a trigger for type 1 leprosy reactions.
| S-EPMC6004287 | biostudies-literature
Project description:BackgroundThe Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs.ObjectiveDescribe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT).Patients and methodsAfter operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial.ResultsSkin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported.Study limitationsLoss of some monthly laboratory sample collection.ConclusionsThere was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.
| S-EPMC6001105 | biostudies-literature