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1.
Acta Trop ; 249: 107019, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952867

RESUMO

INTRODUCTION: Leprosy is a chronic infectious disease that still persists as a public health problem in Brazil. Plantar ulcers are serious complications due to leprosy neuropathy and intensify the isolation and stigma of these individuals. The difficulty in closing these lesions associated with the fetid odor negatively impact the quality of life of people with these lesions. OBJECTIVE: To evaluate the clinical, socioeconomic conditions, degree of satisfaction and quality of life (QoL) of patients after healing of chronic ulcers on feet submitted to orthopedic surgery. METHODOLOGY: This is a qualitative, exploratory, descriptive and observational study carried out with 92 people after surgical treatment of chronic leprosy plantar ulcers. These patients were submitted to a semi-structured questionnaire raising questions of an epidemiological, socioeconomic and perception of quality-of-life order, comparing before and after the surgical procedure. RESULTS: Decrease in indicators - alcohol consumption, tobacco consumption, average monthly cost of analgesic medications, fetid wound odor, foot pain and number of dressings performed weekly; Recurrence of lesions in 55.4 % of cases, related to irregular use or lack of shoes and insoles; Improvement in self-perception of Quality of Life (QoL) in 89.1 % of patients after surgery. CONCLUSION: Orthopedic surgical treatment with resection of plantar bony prominences and skin grafting is an effective therapeutic method for closing chronic plantar ulcers in leprosy, resulting in a decrease in the financial costs employed and in an important improvement in the Quality-of-Life parameters of the individuals undergoing to this procedure. The availability and regular use of shoes and insoles is crucial to prevent recurrence of these injuries.


Assuntos
Úlcera do Pé , Hanseníase , Procedimentos Ortopédicos , Humanos , Úlcera do Pé/cirurgia , Úlcera do Pé/etiologia , Úlcera do Pé/prevenção & controle , Qualidade de Vida , Hanseníase/complicações , Hanseníase/cirurgia , Procedimentos Ortopédicos/efeitos adversos , Cicatrização
2.
PLoS One ; 18(11): e0287665, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38011211

RESUMO

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3ß, 6ß, 16ß-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.


Assuntos
Antiprotozoários , Combretum , Leishmania braziliensis , Leishmaniose Cutânea , Cricetinae , Animais , Camundongos , Pele/patologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Cicatrização , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Camundongos Endogâmicos BALB C
4.
Bauru; s.n; 2023. 87 p. ilus, tab, graf.
Tese em Português | CONASS, SES-SP, HANSEN, HANSENIASE, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP, SESSP-ESPECIALIZACAOSESPROD, SES-SP | ID: biblio-1426350

RESUMO

Úlceras crônicas são definidas quando o processo de reparação do tecido excede o período de 3 meses, dificultando sua cicatrização. Sua etiologia pode ser multifatorial, como a ocorrência de traumas e consequência de patologias, como hanseníase, hipertensão e diabetes. As úlceras abrigam diversos microrganismos colonizadores e residentes que podem tornar-se potenciais agravantes a sua condição clínica, visto sua capacidade de formação de biofilmes e resistência antimicrobiana, diminuindo a eficácia da terapêutica. O objetivo deste trabalho foi determinar os agentes microbianos presentes em úlceras de pacientes com doenças crônicas atendidos no ambulatório de feridas do Instituto Lauro de Souza Lima, avaliar a susceptibilidade antimicrobiana destes isolados e sua capacidade de produção de biofilme, bem como comparar os resultados evidenciados por swab e biópsia e correlacionar os resultados microbiológicos com dados clínicos dos pacientes. Foram coletadas amostras de exsudato por swab e biópsia de úlceras crônicas dos participantes com doenças crônicas. As amostras foram semeadas em ágar sangue, manitol, cetrimide e MacCnkey para posterior identificação microbiana. Também foi desempenhada a determinação da susceptibilidade aos antimicrobianos e capacidade de produção de biofilme dos isolados identificados por swab e biópsia. Foram identificados 47 microrganismos no total, sendo 26 (55%) isolados presentes no swab e 21 (45%) em biópsia. P. aeruginosa, P. mirabilis e S. aureus foram as bactérias comumente prevalentes em ambos os materiais de coleta, com predomínio de P. aeruginosa. Apenas 16 (36%) das bactérias demonstraram capacidade de produzir biofilme, com destaque para o grupo dos gram-positivos (92%) que também exibiram alto perfil de susceptibilidade frente linezolida e vancomicina. Meropenem foi o único fármaco a mostrar eficácia frente as cepas de P. aeruginosa presentes, enquanto o grupo das enterobactérias apresentaram menor resposta frente a amoxicilina com ácido clavulânico. Swab e biópsia apresentaram uma concordância geral de 60%, semelhante ao observado por outros estudos. Tais diferenças podem se dar devido à presença de colonizadores. A cobertura de zinco e bota de Unna foi correlacionada à ausência de sinais flogísticos de infecção. Os dados sociodemográficos mostram prevalência de indíviduos com baixa escolaridade e idade acima de 60 anos. O swab é menos invasivo e mais utilizado devido sua facilidade e baixo custo em relação a biópsia; contudo, deve ser considerado com mais cautela na análise dos resultados microbiológicos.


Chronic wounds are defined when the tissue repair process exceeds the period of 3 months, making it difficult to heal. Its etiology can be multifactorial, such as the occurrence of trauma and consequences of pathologies, such as leprosy, hypertension, and diabetes mellitus. Ulcers harbor several colonizing and resident microorganisms that can become potential aggravating factors for their clinical condition, given their ability to form biofilms and their antimicrobial resistance, decreasing the therapeutic efficacy. This study aimed to determine the microbial agents present in ulcers of patients with chronic conditions treated at the wound clinic of the Instituto Lauro de Souza Lima, to evaluate their antimicrobial susceptibility and ability to produce biofilm, as well as to compare the results evidenced by swab and biopsy and correlate the microbiological results with clinical data of the patients. Exudate samples were collected by swab and biopsy of leg ulcers from participants with chronic diseases. Samples were seeded on sheep blood agar, mannitol, cetrimide and MacConkey agar for subsequent microbial identification. The determination of antimicrobial susceptibility and biofilm production capacity of isolates identified by swab and biopsy was also performed. A total of 47 microorganisms were identified, 26 (55%) of which were isolated from the swab and 21 (45%) from the biopsy. P. aeruginosa, P. mirabilis and S. aureus were the commonly prevalent bacteria in both collection materials, with predominance of P. aeruginosa. Only 16 (36%) bacteria demonstrated the ability to produce biofilm, with emphasis on the gram-positive group (92%) that also exhibited a high profile of susceptibility to linezolid and vancomycin. Meropenem was the only drug to show efficacy against the strains of P. aeruginosa present, while the group of enterobacteria showed less response against amoxicillin with clavulanic acid. Swab and biopsy showed an overall agreement of 60%, similar to that observed by other studies. Such differences may occur due to the presence of colonizers. Zinc coating and Unna boot correlated with the absence of phlogistic signs of infection. Sociodemographic data show a prevalence of individuals with low education and aged over 60 years. The swab is less invasive and more used due to its ease and low cost compared to biopsy; however, it should be considered with more caution in the analysis of microbiological results


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Cicatrização , Biofilmes , Úlcera da Perna/terapia , Ferimentos e Lesões , Biópsia , Resistência Microbiana a Medicamentos , Complicações do Diabetes , Hanseníase/complicações , Anti-Infecciosos
5.
Bauru; s.n; 2023. 31 p. ilus, tab, graf.
Tese em Português | CONASS, SES-SP, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP, SESSP-ESPECIALIZACAOSESPROD, SES-SP | ID: biblio-1426365

RESUMO

A cicatrização de úlceras cutâneas depende de fatores-chave que incluem a interação adequada dos diferentes constituintes celulares da epiderme, derme e tecido subcutâneo. A restauração da barreira epidérmica é altamente eficiente durante o período embrionário, com um relativo decréscimo na vida adulta. Distúrbios sistêmicos, como diabetes e hanseníase, podem comprometer a capacidade de reparação da pele, gerando ulceras crônicas, que são consideradas como relevantes problemas de saúde pública. O presente estudo se propôs a estabelecer parâmetros de eficiência de membranas bioativas, preparadas com o biopolímero quitosana (QT), em associação ao extrato vegetal, madecassoside (MA). Nas preparações obtidas, foram avaliadas características físico-químicas e propriedades antimicrobianas. A biocompatibilidade das preparações, e sua capacidade de promover migração celular, foi testada in vitro em fibroblastos da linhagem NIH/3T3. As membranas foram divididas em grupos: QT 2%; QT/MA 0,10% (QTMA010); QT/MA 0,25% (QTMA025); QT/MA 0,50% (QTMA050). Os grupos foram avaliados em diferentes intervalos de tempo, de 0 a 96 horas (T0, T24, T48, T72, T96). Nossos dados indicam que membranas bioativas, preparadas com quitosana (QT 2%) e madecassoside (MA 0,10%, 0,25%, 0,50%), são biocompatíveis e possuem propriedades físico-químicas adequadas. As preparações contendo associação de ambos os compostos se mostraram superiores à QT. A capacidade de promover migração de fibroblastos, in vitro, foi estatisticamente superior em todos os grupos acrescidos de MA, indicando um papel relevante desse composto em preparações de utilização tópica para cicatrização úlceras cutâneas.


Assuntos
Úlcera Cutânea/terapia , Cicatrização , Quitosana/uso terapêutico , Pele/lesões , Biopolímeros , Técnicas In Vitro , Compostos Fitoquímicos/uso terapêutico
6.
Indian J Dermatol Venereol Leprol ; 88(5): 633-635, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33666040

RESUMO

Pantoea agglomerans is a ubiquitous gram-negative bacterium that has been linked to skin and joint infections secondary to plant injuries. Herein we report a 58-year-old woman who presented with 2 erythematous nodules with purulent discharge on the anterior aspect of the right leg that developed after a penetrating plant injury. The patient was initially treated with amoxicillin-clavulanic acid, cloxacillin and clindamycin without improvement. P. agglomerans was isolated from both exudate and skin biopsy cultures. Healing of the lesions was achieved after the spontaneous release of a retained plant fragment and treatment with cotrimoxazole. Identification of P. agglomerans in persistent exudative lesions should alert the clinician regarding a possible previous plant injury and retained vegetal fragments. Conventional antibiotic treatment and the extraction of retained foreign bodies usually lead to complete resolution.


Assuntos
Pantoea , Infecção dos Ferimentos , Antibacterianos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Plantas , Cicatrização , Infecção dos Ferimentos/diagnóstico , Infecção dos Ferimentos/tratamento farmacológico
8.
Int J Biol Macromol ; 194: 402-411, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34818530

RESUMO

The main objective of this study was to investigate the effects of bacterial cellulose hydrogel (BCH) incorporated into montmorillonite (MMT) and its underlying mechanisms of action on a skin wound healing mouse model following pressure injury model. Komagataeibacter hansenii was used to obtain 5 cm in diameter and 0.8 mm of thickness circular bacterial cellulose (BC) sheets, which were incorporated with MMT by deposition ex-site using a 0.1% MMT suspension (100 rpm for 24 h at 28 °C). Afterward, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM) were used to characterize the bacterial cellulose hydrogel incorporated into montmorillonite (BCH-MMT). The pressure injury model was assessed by macroscopic and histological analysis in male Swiss mice. Both, BC and BCH-MMT, showed a typical FTIR spectrum of cellulosic substrates with pronounces bands around 3344, 2920, 1637, and 1041 cm-1 while microparticles of MMT dispersed uniformly throughout BC were revealed by SEM photographs. Animals treated with BCH-MMT showed significant healing of pressure ulcers as demonstrated by reduced area of redness and spontaneous hyperalgesia, lower amounts of in-site inflammatory cells (to the same level as the positive control Dersani®) and ultimately, complete epidermis re-epithelialization and tissue regeneration. Altogether, these findings suggest that a modified BCH-MMT film could serve as scaffolding for skin tissue engineering and potentially as a novel dressing material for pressure injury.


Assuntos
Bandagens , Bentonita , Celulose , Hidrogéis , Lesão por Pressão , Cicatrização , Animais , Masculino , Camundongos , Bentonita/uso terapêutico , Celulose/uso terapêutico , Hidrogéis/uso terapêutico
9.
Skinmed ; 19(5): 362-368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34861916

RESUMO

Trophic ulcer is a common disability in leprosy, recalcitrant to treatment. Platelet-rich fibrin (PRF) is a new technique for the treatment of trophic ulcer. A study was done to assess the efficacy of PRF in the treatment of trophic ulcer. Twenty-five patients of Wagner's Grade 2 trophic ulcer secondary to leprosy were enrolled. PRF was prepared and applied to ulcers and dressed; this was repeated weekly until complete healing or up to a maximum of six sittings. Ninety percent reduction in mean ulcer volume was seen at 6 weeks, with a mean healing time of 5 weeks. PRF is cost-effective, day care procedure with promising results in trophic ulcers.


Assuntos
Hanseníase , Fibrina Rica em Plaquetas , Dermatopatias , Humanos , Hanseníase/complicações , Úlcera , Cicatrização
10.
J Wound Care ; 30(6): 498-503, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34121439

RESUMO

OBJECTIVE: To describe and quantify the complications arising in consecutive neuropathic patients undergoing partial longitudinal amputations of the foot. METHOD: A retrospective study was conducted with data collected from the medical records of patients monitored at the Insensitive Foot Clinic of the Foot and Ankle Group of our institution who underwent partial amputation of foot rays from 2000 to 2016. RESULTS: A total of 28 patients met the inclusion criteria, with a total of 31 amputated/partially amputated feet. Of these, 18 (58.1%) feet were amputated/partially amputated due to diabetes, seven (22.6%) due to leprosy, two (6.5%) due to alcoholic neuropathy, two (6.5%) secondary to traumatic peripheral nerve injury, and two (6.5%) due to other causes. Fifth ray amputation was the most frequent type (n=12). The cause of amputation was the presence of an infected ulcer in 93.6% of the samples. At a mean follow-up time of 60 months, 13 (41.9%) feet required new amputations-five (38.5%) transtibial, five (38.5%) transmetatarsal, two (15.4%) of the toes, and one (7.7%) at Chopart's joint. Patients with diabetes had a 50.0% reamputation rate. Patients who initially underwent amputation of the fifth ray had a 58.3% reamputation rate. CONCLUSION: Partial longitudinal amputation of the foot in neuropathic patients exhibited a high reoperation rate, especially in patients with diabetes or in patients with initial amputation of the peripheral rays. Declaration of interest: The authors have no conflicts of interest.


Assuntos
Amputação Cirúrgica , Pé Diabético/cirurgia , Pé/cirurgia , Complicações Pós-Operatórias , Amputação Cirúrgica/efeitos adversos , Desbridamento , Humanos , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Cicatrização
11.
Cell Host Microbe ; 29(5): 740-741, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33984275

RESUMO

In a recent Science paper, Jain et al. (2021) discover that a fungus contributes to delayed wound healing in mice and is enriched in inflamed tissue from Crohn's disease patients. This culprit is not a well-known pathogen, but cheese yeast Debaryomyces hansenii, highlighting the importance of further studying fungi-host interactions.


Assuntos
Queijo , Doença de Crohn , Debaryomyces , Animais , Fungos , Humanos , Camundongos , Cicatrização
12.
Immunity ; 54(5): 856-858, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33979584

RESUMO

Intestinal microbiome perturbation characterizes Crohn's disease (CD), though specific contributors to pathophysiology remain elusive. In a recent issue of Science, Jain et al. show that Debaryomyces hansenii impairs intestinal healing in mice via effects on type I interferon signaling and chemokine CCL5 expression in macrophages and that it is also prevalent in the inflamed mucosa of CD patients.


Assuntos
Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Mucosa Intestinal/microbiologia , Cicatrização/imunologia , Animais , Quimiocina CCL5/imunologia , Microbioma Gastrointestinal/imunologia , Humanos , Interferon Tipo I/imunologia , Mucosa Intestinal/imunologia , Macrófagos/imunologia , Camundongos , Micoses/imunologia , Micoses/microbiologia , Saccharomycetales/imunologia , Transdução de Sinais/imunologia
14.
Science ; 371(6534): 1102-1103, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33707253
15.
J Dermatolog Treat ; 32(8): 1026-1030, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32068454

RESUMO

BACKGROUND: Chronic plantar ulcers in leprosy (CPUL) occur in areas that have a sensory and an autonomic nerve impairment where the wound healing takes longer. Framycetin gauze dressing (FGD) is best used in the wound healing process during the inflammatory phase because it contains antibiotics. Epigallocatechin gallate (EGCG) is the highest component in the extract of green tea that can accelerate blood vessel formation, has an anti-inflammatory effect, and reepithelialization. OBJECTIVE: To investigate the effect of topical EGCG 1% on the healing of CPUL. MATERIALS AND METHODS: An analytical experimental approach comparing the topical EGCG 1% and FGD applied every 3 days up to 8 weeks on the healing of CPUL. Size of the ulcers, side effects and possible complications from both approaches were monitored weekly. RESULTS: Ulcer healing in the EGCG group was significantly better than the FGD group with significant clinical and statistical differences (p < .032). There were no side effects in both the study groups. Complications, such as an increase in the size of the ulcer, were noted in one subject in the control group. This may have been caused by FGD and claw foot condition. CONCLUSIONS: EGCG 1% is more effective than FGD in accelerating the healing process of CPUL.


Assuntos
Catequina , Úlcera do Pé , Hanseníase , Catequina/análogos & derivados , Catequina/uso terapêutico , Úlcera do Pé/tratamento farmacológico , Úlcera do Pé/etiologia , Humanos , Hanseníase/complicações , Cicatrização
16.
PLoS Negl Trop Dis ; 14(6): e0008393, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32598386

RESUMO

BACKGROUND: Non-healing plantar ulcers are one of the significant causes of disability in leprosy patients. Plantar ulcers often take months or years to heal, affecting the patient's quality of life. Presence of comorbid conditions in these patients can delay wound healing. The study aimed to evaluate the role of associated comorbid conditions as risk factors in ulcer healing. METHODOLOGY/PRINCIPAL FINDINGS: A total of 66 leprosy patients with plantar ulcers registered at LEPRA Society-Blue Peter Public Health and Research Center (BPHRC), Hyderabad, India from June 2018 to June 2019 were studied. Comprehensive clinical assessment was done, including screening for comorbid conditions and treated as per the recommended guidelines. About two-thirds of the participants were aged 50 and above, of which more than half were illiterates, and 93.5% were living below the poverty line. Majority of ulcers were seen on the forefoot; with the head of meta-tarsal bone 27 (41.6%) as the commonest site, followed by calcaneum 23 (38.3%) and great toe 10 (16.6%). Mean ulcer depth was 0.61 (0.57) cm, the area was 5.24 (6.73) cm2 and ulcer volume was 4.72 (14.33) cm3. Ulcer dimensions were significantly associated with low body mass index, hypertension and smoking. CONCLUSIONS/SIGNIFICANCE: Identifying the risk factors delaying wound healing and detailed assessment of ulcers are of profound importance to predict the outcome of plantar ulcers in leprosy patients. The study findings indicate the need for better policies by the leprosy control program for the comprehensive management of plantar ulcers.


Assuntos
Comorbidade , Úlcera do Pé/complicações , Hanseníase/complicações , Adulto , Idoso , Estudos Transversais , Feminino , , Úlcera do Pé/epidemiologia , Humanos , Índia/epidemiologia , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Pobreza , Fatores de Risco , Cicatrização
17.
Expert Rev Clin Pharmacol ; 13(4): 391-401, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32310683

RESUMO

INTRODUCTION: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. AREAS COVERED: We review BU drug treatment - in vitro, in vivo and clinical trials (PubMed: '(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).' We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. EXPERT OPINION: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer.


Assuntos
Antibacterianos/farmacologia , Úlcera de Buruli/tratamento farmacológico , Mycobacterium ulcerans/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Úlcera de Buruli/microbiologia , Reposicionamento de Medicamentos , Quimioterapia Combinada , Humanos , Macrolídeos/metabolismo , Mycobacterium ulcerans/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Cicatrização/efeitos dos fármacos
18.
Lancet ; 395(10232): 1259-1267, 2020 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-32171422

RESUMO

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac.


Assuntos
Úlcera de Buruli/tratamento farmacológico , Claritromicina/administração & dosagem , Rifampina/administração & dosagem , Estreptomicina/administração & dosagem , Administração Oral , Adolescente , Adulto , Antibacterianos , Benin , Criança , Claritromicina/efeitos adversos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Quimioterapia Combinada , Feminino , Gana , Humanos , Masculino , Rifampina/efeitos adversos , Estreptomicina/efeitos adversos , Cicatrização/efeitos dos fármacos , Adulto Jovem
19.
Adv Skin Wound Care ; 33(2): 1-6, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31972587

RESUMO

BACKGROUND: Chronic trophic ulcers (CTUs), especially those located over the plantar region, are a leading cause of deformity and disability in patients with leprosy. Despite the various treatment modalities available, CTUs can be chronic and refractory to treatment. The successful use of topical insulin in various types of wounds led researchers to evaluate its safety and efficacy in the treatment of plantar CTUs. METHODS: Forty-two patients who had completed a multidrug treatment for leprosy were recruited and randomized into two groups. In the test group, 23 patients received 10 units (0.1 mL) of topical insulin (Actrapid) in 1 mL of normal saline twice daily over treated areas. The placebo group (n = 19) received topical normal saline only. The primary end point was the proportion of patients with complete wound closure by 12 weeks. Secondary end points included time to healing, wound area reduction, Physician Global Assessment of Efficacy scores, and Dermatology Life Quality Index scores at the end of 12 weeks. RESULTS: The majority of CTUs (80%) were situated over the forefoot; the metatarsal head of the hallux was the most common site (86%). Wound healing was faster (0.61 ± 0.31 vs 0.14 ± 0.42 cm per week, P < .0001), and the number of days to complete healing was significantly shorter in the test group compared with the placebo group (31.5 ± 17.6 vs 44.3 ± 16.2 days, P = .02). The only observed adverse effect in the test group was white granular deposits over the CTU (n = 10). CONCLUSIONS: Topical insulin therapy may be a safe, efficacious, cheap, and easily available treatment option in CTUs among patients with leprosy.


Assuntos
Úlcera do Pé/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Regular de Porco/administração & dosagem , Hanseníase/complicações , Administração Tópica , Adulto , Doença Crônica , Feminino , Úlcera do Pé/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Cicatrização
20.
Indian J Dermatol Venereol Leprol ; 86(3): 262-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31997794

RESUMO

BACKGROUND: Trophic ulcers secondary to leprosy pose a great stigma to patients and remain a challenge to the treating dermatologists. Platelet-rich plasma (PRP) introduces growth factors directly into the wound and aids in rapid healing. The role of PRP in the treatment of trophic ulcers in leprosy patients has not yet been established by randomized controlled trials. AIMS: To study the effectiveness and safety of autologous PRP therapy with total contact casting versus total contact casting alone in the treatment of trophic ulcers in leprosy. METHODS: In an observer-blind, randomized (1:1) controlled study, 118 patients were enrolled. PRP was prepared by the manual double-spin method (1600 rpm for 10 min followed by 4000 rpm for 10 min). After wound bed preparation, activated PRP was injected intra- and perilesionally, and platelet-poor plasma gel was applied over the ulcer bed. Occlusive dressings and total contact casting were then applied in Group A, and only total contact casting was applied in Group B. The same procedure was repeated every 2 weeks for 8 weeks. RESULTS: In all, 56 patients were analyzable in Group A and 52 in Group B. The surface area of the ulcer decreased significantly from first follow-up onward in both the groups (P < 0.001 in both the groups). Intergroup comparison showed that the reduction in the surface area of the ulcer was significantly more in Group A than in Group B from the first follow-up onward (P = 0.038) and the difference was maintained till the fifth follow-up (P < 0.001). At the end of the study, 91.10 ± 9.65% ulcer surface area reduction had occurred in Group A, whereas it was 79.77 ± 17.91% in Group B (P < 0.001). Trophic ulcers healed completely more often in paucibacillary leprosy patients (P < 0.001) and in those with a lower initial surface area of the ulcer (P < 0.001). LIMITATION: Short duration of treatment (8 weeks). CONCLUSION: PRP combined with total contact casting accelerates the healing of trophic ulcers of leprosy and is more effective than total contact casting alone. Complete remission is more likely to occur when the duration and surface area of ulcer are less and in the paucibacillary spectrum.


Assuntos
Hanseníase/diagnóstico , Hanseníase/terapia , Plasma Rico em Plaquetas , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Transplante Autólogo/métodos , Resultado do Tratamento , Cicatrização/fisiologia , Adulto Jovem
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